Browsing by Author "Bhatti, Jasvinder Singh"

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Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches
(Elsevier Inc., 2023-09-20T00:00:00) Bhattacharya, Srinjan; Mahato, Rahul Kumar; Singh, Satwinder; Bhatti, Gurjit Kaur; Mastana, Sarabjit Singh; Bhatti, Jasvinder Singh
Thyroid cancer continues to exhibit a rising incidence globally, predominantly affecting women. Despite stable mortality rates, the unique characteristics of thyroid carcinoma warrant a distinct approach. Differentiated thyroid cancer, comprising most cases, is effectively managed through standard treatments such as thyroidectomy and radioiodine therapy. However, rarer variants, including anaplastic thyroid carcinoma, necessitate specialized interventions, often employing targeted therapies. Although these drugs focus on symptom management, they are not curative. This review delves into the fundamental modulators of thyroid cancers, encompassing genetic, epigenetic, and non-coding RNA factors while exploring their intricate interplay and influence. Epigenetic modifications directly affect the expression of causal genes, while long non-coding RNAs impact the function and expression of micro-RNAs, culminating in tumorigenesis. Additionally, this article provides a concise overview of the advantages and disadvantages associated with pharmacological and non-pharmacological therapeutic interventions in thyroid cancer. Furthermore, with technological advancements, integrating modern software and computing into healthcare and medical practices has become increasingly prevalent. Artificial intelligence and machine learning techniques hold the potential to predict treatment outcomes, analyze data, and develop personalized therapeutic approaches catering to patient specificity. In thyroid cancer, cutting-edge machine learning and deep learning technologies analyze factors such as ultrasonography results for tumor textures and biopsy samples from fine needle aspirations, paving the way for a more accurate and effective therapeutic landscape in the near future. � 2023 The Author(s)
Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach
(John Wiley and Sons Inc, 2023-10-04T00:00:00) Goyal, Falak; Chattopadhyay, Anandini; Navik, Umashanker; Jain, Aklank; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
mRNA vaccines have long been recognized for their ability to induce robust immune responses. The discovery that mRNA vaccines may also contribute to antitumor immunity has made them a promising therapeutic approach against cancer. Recent advances in understanding of immune system are precious in developing therapeutic strategies that target pathways involved in tumor survival and progression, leading to the most reliable therapeutic strategies in cancer treatment history. Among all traditional cancer treatments, cancer immunotherapies are less toxic and more effective, even in advanced or recurrent stages of cancer. Recent advancements in genomics and machine learning algorithms give new insight into vaccine development. mRNA vaccines are designed to interfere with stimulator of interferon genes (STING) and tumor-infiltrating lymphocytes pathways, activating more CD8+ T-cells involved in destroying tumor cells and inhibiting tumor growth. A stronger immune response can be achieved by incorporating immunological adjuvants alongside mRNA. Nonformulated or vehicle-based mRNA vaccines, when combined with adjuvants, efficiently express tumor antigens through antigen-presenting cells and stimulate both innate and adaptive immune responses. Codelivery with additional immunotherapeutic agents, such as checkpoint inhibitors, further enhances the efficacy of mRNA vaccines. This article focuses on the current clinical approaches and challenges to consider when developing mRNA-based vaccine technology for cancer treatment. � 2023 Wiley-VCH GmbH.
ALK and ERBB2 Protein Inhibition is Involved in the Prevention of Lung Cancer Development by Vincamine
(Bentham Science Publishers, 2023-04-13T00:00:00) Verma, Aarti; Yadav, Poonam; Rajput, Sonu; Verma, Saloni; Arora, Sahil; Kumar, Raj; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
Background: According to the WHO report of 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. Objective: To find the potential targets of vincamine using a network pharmacology approach and docking studies and to evaluate the anti-cancer effect of vincamine on A549 cell line. Methods: Hence, in the present study, we explored the anti-cancer potential of vincamine by using network pharma-cology, molecular docking, and in vitro approaches. Network pharmacology demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. Results: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dose-dependent (0-500 ?M) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 ??. The wound-healing assay showed that vincamine treatment (150 and 300 ?M) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. Conclusion: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects. � 2023 Bentham Science Publishers.
Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity
(Elsevier Inc., 2023-09-24T00:00:00) Jaiswal, Aiswarya; Rawat, Pushkar Singh; Singh, Sumeet Kumar; Bhatti, Jasvinder Singh; Khurana, Amit; Navik, Umashanker
The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limited due to its cardiotoxicity, including congestive heart failure, alterations in myocardial structure, arrhythmia, and left ventricular dysfunction. Dox causes cardiotoxicity via various mechanisms, including oxidative stress, mitochondrial dysfunctioning, deranged Ca2+ homeostasis, inflammation, fibrosis, downregulating AMPK, etc. Betaine is a zwitterion-based drug known as N, N, N trimethylglycine that regulates the methionine cycle and homocysteine (a risk factor for cardiovascular disease) detoxification through betaine-homocysteine methyltransferases. Betaine is nontoxic and has several beneficial effects in different disease models. Betaine treatment decreases the amyloid ? generation, reduces obesity, improves steatosis and fibrosis, and activates AMP-activated protein kinase (AMPK). Further, betaine downregulates 8?hydroxy-2-deoxyguanosine, malondialdehyde, and upregulates catalases, glutathione peroxidase, and superoxide dismutase activity. Therefore, we hypothesized that betaine might be a rational drug candidate to effectively combat Dox-associated oxidative stress, inflammation, and mitochondrial dysfunction. � 2023 The Author(s)
Clinical Strategies and Therapeutics for Human Monkeypox Virus: A Revised Perspective on Recent Outbreaks
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-07-12T00:00:00) Ghosh, Nilanjan; Chacko, Leena; Vallamkondu, Jayalakshmi; Banerjee, Tanmoy; Sarkar, Chandrima; Singh, Birbal; Kalra, Rajkumar Singh; Bhatti, Jasvinder Singh; Kandimalla, Ramesh; Dewanjee, Saikat
An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies. � 2023 by the authors.
Current development of 1,2,3-triazole derived potential antimalarial scaffolds: Structure- activity relationship (SAR) and bioactive compounds
(Elsevier Masson s.r.l., 2023-07-30T00:00:00) Abdul Rahman, S. Maheen; Bhatti, Jasvinder Singh; Thareja, Suresh; Monga, Vikramdeep
Malaria is among one of the most devastating and deadliest parasitic disease in the world claiming millions of lives every year around the globe. It is a mosquito-borne infectious disease caused by various species of the parasitic protozoan of the genus Plasmodium. The indiscriminate exploitation of the clinically used antimalarial drugs led to the development of various drug-resistant and multidrug-resistant strains of plasmodium which severely reduces the therapeutic effectiveness of most frontline medicines. Therefore, there is urgent need to develop novel structural classes of antimalarial agents acting with unique mechanism of action(s). In this context, design and development of hybrid molecules containing pharmacophoric features of different lead molecules in a single entity represents a unique strategy for the development of next-generation antimalarial drugs. Research efforts by the scientific community over the past few years has led to the identification and development of several heterocyclic small molecules as antimalarial agents with high potency, less toxicity and desired efficacy. Triazole derivatives have become indispensable units in the medicinal chemistry due to their diverse spectrum of biological profiles and many triazole based hybrids and conjugates have demonstrated potential in vitro and in vivo antimalarial activities. The manuscript compiled recent developments in the medicinal chemistry of triazole based small heterocyclic molecules as antimalarial agents and discusses various reported biologically active compounds to lay the groundwork for the rationale design and discovery of triazole based antimalarial compounds. The article emphasised on biological activities, structure activity relationships, and molecular docking studies of various triazole based hybrids with heterocycles such as quinoline, artemisinins, naphthyl, naphthoquinone, etc. as potential antimalarial agents which could act on the dual stage and multi stage of the parasitic life cycle. � 2023 Elsevier Masson SAS
Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management
(Elsevier Masson s.r.l., 2021-05-13T00:00:00) Rawat, Pushkar Singh; Jaiswal, Aiswarya; Khurana, Amit; Bhatti, Jasvinder Singh; Navik, Umashanker
Doxorubicin (Dox) is a secondary metabolite of the mutated strain of Streptomyces peucetius var. Caesius and belongs to the anthracyclines family. The anti-cancer activity of Dox is mainly exerted through the DNA intercalation and inhibiting topoisomerase II enzyme in fast-proliferating tumors. However, Dox causes cumulative and dose-dependent cardiotoxicity, which results in increased risks of mortality among cancer patients and thus limiting its wide clinical applications. There are several mechanisms has been proposed for doxorubicin-induced cardiotoxicity and oxidative stress, free radical generation and apoptosis are most widely reported. Apart from this, other mechanisms are also involved in Dox-induced cardiotoxicity such as impaired mitochondrial function, a perturbation in iron regulatory protein, disruption of Ca2+ homeostasis, autophagy, the release of nitric oxide and inflammatory mediators and altered gene and protein expression that involved apoptosis. Dox also causes downregulation of DNA methyltransferase 1 (DNMT1) enzyme activity which leads to a reduction in the DNA methylation process. This hypomethylation causes dysregulation in the mitochondrial genes like peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1-alpha (PGC-1?), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) unit in the heart. Apart from DNA methylation, Dox treatment also alters the micro RNAs levels and histone deacetylase (HDAC) activity. Therefore, in the current review, we have provided a detailed update on the current understanding of the pathological mechanisms behind the well-known Dox-induced cardiotoxicity. Further, we have provided some of the most plausible pharmacological strategies which have been tested against Dox-induced cardiotoxicity. � 2021 The Authors
Dysregulated autophagy: A key player in the pathophysiology of type 2 diabetes and its complications
(Elsevier B.V., 2023-02-14T00:00:00) Sehrawat, Abhishek; Mishra, Jayapriya; Mastana, Sarabjit Singh; Navik, Umashanker; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Autophagy is essential in regulating the turnover of macromolecules via removing damaged organelles, misfolded proteins in various tissues, including liver, skeletal muscles, and adipose tissue to maintain the cellular homeostasis. In these tissues, a specific type of autophagy maintains the accumulation of lipid droplets which is directly related to obesity and the development of insulin resistance. It appears to play a protective role in a normal physiological environment by eliminating the invading pathogens, protein aggregates, and damaged organelles and generating energy and new building blocks by recycling the cellular components. Ageing is also a crucial modulator of autophagy process. During stress conditions involving nutrient deficiency, lipids excess, hypoxia etc., autophagy serves as a pro-survival mechanism by recycling the free amino acids to maintain the synthesis of proteins. The dysregulated autophagy has been found in several ageing associated diseases including type 2 diabetes (T2DM), cancer, and neurodegenerative disorders. So, targeting autophagy can be a promising therapeutic strategy against the progression to diabetes related complications. Our article provides a comprehensive outline of understanding of the autophagy process, including its types, mechanisms, regulation, and role in the pathophysiology of T2DM and related complications. We also explored the significance of autophagy in the homeostasis of ?-cells, insulin resistance (IR), clearance of protein aggregates such as islet amyloid polypeptide, and various insulin-sensitive tissues. This will further pave the way for developing novel therapeutic strategies for diabetes-related complications. � 2023 Elsevier B.V.
Emerging role of non?coding RNA in health and disease
(Springer, 2021-04-21T00:00:00) Bhatti, Gurjit Kaur; Khullar, Naina; Sidhu, Inderpal Singh; Navik, Uma Shanker; Reddy, Arubala P.; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Human diseases have always been a significant turf of concern since the origin of mankind. It is cardinal to know the cause, treatment, and cure for every disease condition. With the advent and advancement in technology, the molecular arena at the microscopic level to study the mechanism, progression, and therapy is more rational and authentic pave than a macroscopic approach. Non-coding RNAs (ncRNAs) have now emerged as indispensable players in the diagnosis, development, and therapeutics of every abnormality concerning physiology, pathology, genetics, epigenetics, oncology, and developmental diseases. This is a comprehensive attempt to collate all the existing and proven strategies, techniques, mechanisms of genetic disorders including Silver Russell Syndrome, Fascio- scapula humeral muscular dystrophy, cardiovascular diseases (atherosclerosis, cardiac fibrosis, hypertension, etc.), neurodegenerative diseases (Spino-cerebral ataxia type 7, Spino-cerebral ataxia type 8, Spinal muscular atrophy, Opitz-Kaveggia syndrome, etc.) cancers (cervix, breast, lung cancer, etc.), and infectious diseases (viral) studied so far. This article encompasses discovery, biogenesis, classification, and evolutionary prospects of the existence of this junk RNA along with the integrated networks involving chromatin remodelling, dosage compensation, genome imprinting, splicing regulation, post-translational regulation and proteomics. In conclusion, all the major human diseases are discussed with a facilitated technology transfer, advancements, loopholes, and tentative future research prospects have also been proposed. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Genomic diversity and differentiation of Alu insertion polymorphisms in a native British and four South Asian migrant populations
(Taylor and Francis Ltd., 2023-02-14T00:00:00) Beaumont, Rebekah; Akam, Liz; Singh, Puneetpal; Bhatti, Jasvinder Singh; Mastana, Sarabjit
Background: Alu insertions are bi-allelic and primate-specific, this makes them a useful marker for studying genetic variation, migration patterns, forensic analyses, paternity, and evolutionary heritage; however, specific population studies are limited. Aim: The objective of this study is to document the level and extent of genetic variation at 39 different Alu loci in five populations (British, Indian Punjabi, Indian Gujarati, Pakistani, and Bangladeshi) from the East Midlands region of the UK. Genetic data on migrant populations is currently limited. Subjects and Methods: DNA samples (n = 543) were analysed for 39 Alu insertion polymorphisms using specific primers and standard protocols. Data were analysed for population and forensic genetic parameters. Results: All studied Alus were polymorphic in the British White population while South Asian migrant populations had a variable number of loci which were monomorphic. Highest heterozygosities and lowest match probabilities were observed in the British sample, while the Bangladeshi sample had the lowest heterozygosity and higher match probability. Conclusion: The analysed Alus insertions (TPA25, Ya5NBC123, Ya5NBC182, Ya5NBC241, and Ya5NBC242) are highly polymorphic and variable among migrant populations. These loci could be useful for population genomic and differentiation studies. � 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021
(Elsevier B.V., 2023-06-23T00:00:00) Ong, Kanyin Liane; Stafford, Lauryn K.; McLaughlin, Susan A.; Boyko, Edward J.; Vollset, Stein Emil; Smith, Amanda E.; Dalton, Bronte E.; Duprey, Joe; Cruz, Jessica A.; Hagins, Hailey; Lindstedt, Paulina A.; Aali, Amirali; Abate, Yohannes Habtegiorgis; Abate, Melsew Dagne; Abbasian, Mohammadreza; Abbasi-Kangevari, Zeinab; Abbasi-Kangevari, Mohsen; ElHafeez, Samar Abd; Abd-Rabu, Rami; Abdulah, Deldar Morad; Abdullah, Abu Yousuf Md; Abedi, Vida; Abidi, Hassan; Aboagye, Richard Gyan; Abolhassani, Hassan; Abu-Gharbieh, Eman; Abu-Zaid, Ahmed; Adane, Tigist Demssew; Adane, Denberu Eshetie; Addo, Isaac Yeboah; Adegboye, Oyelola A.; Adekanmbi, Victor; Adepoju, Abiola Victor; Adnani, Qorinah Estiningtyas Sakilah; Afolabi, Rotimi Felix; Agarwal, Gina; Aghdam, Zahra Babaei; Agudelo-Botero, Marcela; Arriagada, Constanza Elizabeth Aguilera; Agyemang-Duah, Williams; Ahinkorah, Bright Opoku; Ahmad, Danish; Ahmad, Rizwan; Ahmad, Sajjad; Ahmad, Aqeel; Ahmadi, Ali; Ahmadi, Keivan; Ahmed, Ayman; Ahmed, Ali; Ahmed, Luai A.; Ahmed, Syed Anees; Ajami, Marjan; Akinyemi, Rufus Olusola; Al Hamad, Hanadi; Al Hasan, Syed Mahfuz; AL-Ahdal, Tareq Mohammed Ali; Alalwan, Tariq A.; Al-Aly, Ziyad; AlBataineh, Mohammad T.; Alcalde-Rabanal, Jacqueline Elizabeth; Alemi, Sharifullah; Ali, Hassam; Alinia, Tahereh; Aljunid, Syed Mohamed; Almustanyir, Sami; Al-Raddadi, Rajaa M.; Alvis-Guzman, Nelson; Amare, Firehiwot; Ameyaw, Edward Kwabena; Amiri, Sohrab; Amusa, Ganiyu Adeniyi; Andrei, Catalina Liliana; Anjana, Ranjit Mohan; Ansar, Adnan; Ansari, Golnoosh; Ansari-Moghaddam, Alireza; Anyasodor, Anayochukwu Edward; Arabloo, Jalal; Aravkin, Aleksandr Y.; Areda, Demelash; Arifin, Hidayat; Arkew, Mesay; Armocida, Benedetta; Arnlov, Johan; Artamonov, Anton A.; Arulappan, Judie; Aruleba, Raphael Taiwo; Arumugam, Ashokan; Aryan, Zahra; Asemu, Mulu Tiruneh; Asghari-Jafarabadi, Mohammad; Askari, Elaheh; Asmelash, Daniel; Astell-Burt, Thomas; Athar, Mohammad; Athari, Seyyed Shamsadin; Atout, Maha Moh'd Wahbi; Avila-Burgos, Leticia; Awaisu, Ahmed; Azadnajafabad, Sina; Darshan, B.B.; Babamohamadi, Hassan; Badar, Muhammad; Badawi, Alaa; Badiye, Ashish D.; Baghcheghi, Nayereh; Bagheri, Nasser; Bagherieh, Sara; Bah, Sulaiman; Bahadory, Saeed; Bai, Ruhai; Baig, Atif Amin; Baltatu, Ovidiu Constantin; Baradaran, Hamid Reza; Barchitta, Martina; Bardhan, Mainak; Barengo, Noel C.; Barnighausen, Till Winfried; Barone, Mark Thomaz Ugliara; Barone-Adesi, Francesco; Barrow, Amadou; Bashiri, Hamideh; Basiru, Afisu; Basu, Sanjay; Basu, Saurav; Batiha, Abdul-Monim Mohammad; Batra, Kavita; Bayih, Mulat Tirfie; Bayileyegn, Nebiyou Simegnew; Behnoush, Amir Hossein; Bekele, Alehegn Bekele; Belete, Melaku Ashagrie; Belgaumi, Uzma Iqbal; Belo, Luis; Bennett, Derrick A.; Bensenor, Isabela M.; Berhe, Kidanemaryam; Berhie, Alemshet Yirga; Bhaskar, Sonu; Bhat, Ajay Nagesh; Bhatti, Jasvinder Singh; Bikbov, Boris; Bilal, Faiq; Bintoro, Bagas Suryo; Bitaraf, Saeid; Bitra, Veera R.; Bjegovic-Mikanovic, Vesna; Bodolica, Virginia; Boloor, Archith; Brauer, Michael; Brazo-Sayavera, Javier; Brenner, Hermann; Butt, Zahid A.; Calina, Daniela; Campos, Luciana Aparecida; Campos-Nonato, Ismael R.; Cao, Yin; Cao, Chao; Car, Josip; Carvalho, Marcia; Castaneda-Orjuela, Carlos A.; Catala-Lopez, Ferran; Cerin, Ester; Chadwick, Joshua; Chandrasekar, Eeshwar K.; Chanie, Gashaw Sisay; Charan, Jaykaran; Chattu, Vijay Kumar; Chauhan, Kirti; Cheema, Huzaifa Ahmad; Abebe, Endeshaw Chekol; Chen, Simiao; Cherbuin, Nicolas; Chichagi, Fatemeh; Chidambaram, Saravana Babu; Cho, William C. S.; Choudhari, Sonali Gajanan; Chowdhury, Rajiv; Chowdhury, Enayet Karim; Chu, Dinh-Toi; Chukwu, Isaac Sunday; Chung, Sheng-Chia; Coberly, Kaleb; Columbus, Alyssa; Contreras, Daniela; Cousin, Ewerton; Criqui, Michael H.; Cruz-Martins, Natalia; Cuschieri, Sarah; Dabo, Bashir; Dadras, Omid; Dai, Xiaochen; Damasceno, Albertino Antonio Moura; Dandona, Rakhi; Dandona, Lalit; Das, Saswati; Dascalu, Ana Maria; Dash, Nihar Ranjan; Dashti, Mohsen; Davila-Cervantes, Claudio Alberto; De la Cruz-Gongora, Vanessa; Debele, Gebiso Roba; Delpasand, Kourosh; Demisse, Fitsum Wolde; Demissie, Getu Debalkie; Deng, Xinlei; Denova-Gutierrez, Edgar; Deo, Salil V.; Dervi�evi?, Emina; Desai, Hardik Dineshbhai; Desale, Aragaw Tesfaw; Dessie, Anteneh Mengist; Desta, Fikreab; Dewan, Syed Masudur Rahman; Dey, Sourav; Dhama, Kuldeep; Dhimal, Meghnath; Diao, Nancy; Diaz, Daniel; Dinu, Monica; Diress, Mengistie; Djalalinia, Shirin; Doan, Linh Phuong; Dongarwar, Deepa; dos Santos Figueiredo, Francisco Winter; Duncan, Bruce B.; Dutta, Siddhartha; Dziedzic, Arkadiusz Marian; Edinur, Hisham Atan; Ekholuenetale, Michael; Ekundayo, Temitope Cyrus; Elgendy, Islam Y.; Elhadi, Muhammed; El-Huneidi, Waseem; Elmeligy, Omar Abdelsadek Abdou; Elmonem, Mohamed A.; Endeshaw, Destaw; Esayas, Hawi Leul; Eshetu, Habitu Birhan; Etaee, Farshid; Fadhil, Ibtihal; Fagbamigbe, Adeniyi Francis; Fahim, Ayesha; Falahi, Shahab; Faris, MoezAlIslam Ezzat Mahmoud; Farrokhpour, Hossein; Farzadfar, Farshad; Fatehizadeh, Ali; Fazli, Ghazal; Feng, Xiaoqi; Ferede, Tomas Y.; Fischer, Florian; Flood, David; Forouhari, Ali; Foroumadi, Roham; Koudehi, Masoumeh Foroutan; Gaidhane, Abhay Motiramji; Gaihre, Santosh; Gaipov, Abduzhappar; Galali, Yaseen; Ganesan, Balasankar; Garcia-Gordillo, M.A.; Gautam, Rupesh K.; Gebrehiwot, Mesfin; Gebrekidan, Kahsu Gebrekirstos; Gebremeskel, Teferi Gebru; Getacher, Lemma; Ghadirian, Fataneh; Ghamari, Seyyed-Hadi; Nour, Mohammad Ghasemi; Ghassemi, Fariba; Golechha, Mahaveer; Goleij, Pouya; Golinelli, Davide; Gopalani, Sameer Vali; Guadie, Habtamu Alganeh; Guan, Shi-Yang; Gudayu, Temesgen Worku; Guimaraes, Rafael Alves; Guled, Rashid Abdi; Gupta, Rajeev; Gupta, Kartik; Gupta, Veer Bala; Gupta, Vivek Kumar; Gyawali, Bishal; Haddadi, Rasool; Hadi, Najah R.; Haile, Teklehaimanot Gereziher; Hajibeygi, Ramtin; Haj-Mirzaian, Arvin; Halwani, Rabih; Hamidi, Samer; Hankey, Graeme J.; Hannan, Md Abdul; Haque, Shafiul; Harandi, Hamid; Harlianto, Netanja I.; Mahmudul Hasan, S.M.; Hasan, Syed Shahzad; Hasani, Hamidreza; Hassanipour, Soheil; Hassen, Mohammed Bheser; Haubold, Johannes; Hayat, Khezar; Heidari, Golnaz; Heidari, Mohammad; Hessami, Kamran; Hiraike, Yuta; Holla, Ramesh; Hossain, Sahadat; Hossain, Md Shakhaoat; Hosseini, Mohammad-Salar; Hosseinzadeh, Mehdi; Hosseinzadeh, Hassan; Huang, Junjie; Huda, Md Nazmul; Hussain, Salman; Huynh, Hong-Han; Hwang, Bing-Fang; Ibitoye, Segun Emmanuel; Ikeda, Nayu; Ilic, Irena M.; Ilic, Milena D.; Inbaraj, Leeberk Raja; Iqbal, Afrin; Islam, Sheikh Mohammed Shariful; Islam, Rakibul M.; Ismail, Nahlah Elkudssiah; Iso, Hiroyasu; Isola, Gaetano; Itumalla, Ramaiah; Iwagami, Masao; Iwu, Chidozie C. D.; Iyamu, Ihoghosa Osamuyi; Iyasu, Assefa N.; Jacob, Louis; Jafarzadeh, Abdollah; Jahrami, Haitham; Jain, Rajesh; Jaja, Chinwe; Jamalpoor, Zahra; Jamshidi, Elham; Janakiraman, Balamurugan; Jayanna, Krishnamurthy; Jayapal, Sathish Kumar; Jayaram, Shubha; Jayawardena, Ranil; Jebai, Rime; Jeong, Wonjeong; Jin, Yinzi; Jokar, Mohammad; Jonas, Jost B.; Joseph, Nitin; Joseph, Abel; Joshua, Charity Ehimwenma; Joukar, Farahnaz; Jozwiak, Jacek Jerzy; Kaambwa, Billingsley; Kabir, Ali; Kabthymer, Robel Hussen; Kadashetti, Vidya; Kahe, Farima; Kalhor, Rohollah; Kandel, Himal; Karanth, Shama D.; Karaye, Ibraheem M.; Karkhah, Samad; Katoto, Patrick D. M. C.; Kaur, Navjot; Kazemian, Sina; Kebede, Sewnet Adem; Khader, Yousef Saleh; Khajuria, Himanshu; Khalaji, Amirmohammad; Khan, Moien A. B.; Khan, Maseer; Khan, Ajmal; Khanal, Saval; Khatatbeh, Moawiah Mohammad; Khater, Amir M.; Khateri, Sorour; Khorashadizadeh, Fatemeh; Khubchandani, Jagdish; Kibret, Biruk Getahun; Kim, Min Seo; Kimokoti, Ruth W.; Kisa, Adnan; Kivimaki, Mika; Kolahi, Ali-Asghar; Komaki, Somayeh; Kompani, Farzad; Koohestani, Hamid Reza; Korzh, Oleksii; Kostev, Karel; Kothari, Nikhil; Koyanagi, Ai; Krishan, Kewal; Krishnamoorthy, Yuvaraj; Defo, Barthelemy Kuate; Kuddus, Mohammed; Kuddus, Md Abdul; Kumar, Rakesh; Kumar, Harish; Kundu, Satyajit; Kurniasari, Maria Dyah; Kuttikkattu, Ambily; Vecchia, Carlo La; Lallukka, Tea; Larijani, Bagher; Larsson, Anders O.; Latief, Kamaluddin; Lawal, Basira Kankia; Le, Thao Thi Thu; Le, Trang Thi Bich; Lee, Shaun Wen Huey; Lee, Munjae; Lee, Wei-Chen; Lee, Paul H.; Lee, Sang-Woong; Lee, Seung Won; Legesse, Samson Mideksa; Lenzi, Jacopo; Li, Yongze; Li, Ming-Chieh; Lim, Stephen S.; Lim, Lee-Ling; Liu, Xuefeng; Liu, Chaojie; Lo, Chun-Han; Lopes, Graciliana; Lorkowski, Stefan; Lozano, Rafael; Lucchetti, Giancarlo; Maghazachi, Azzam A.; Mahasha, Phetole Walter; Mahjoub, Soleiman; Mahmoud, Mansour Adam; Mahmoudi, Razzagh; Mahmoudimanesh, Marzieh; Mai, Anh Tuan; Majeed, Azeem; Sanaye, Pantea Majma; Makris, Konstantinos Christos; Malhotra, Kashish; Malik, Ahmad Azam; Malik, Iram; Mallhi, Tauqeer Hussain; Malta, Deborah Carvalho; Mamun, Abdullah A.; Mansouri, Borhan; Marateb, Hamid Reza; Mardi, Parham; Martini, Santi; Martorell, Miquel; Marzo, Roy Rillera; Masoudi, Reza; Masoudi, Sahar; Mathews, Elezebeth; Maugeri, Andrea; Mazzaglia, Giampiero; Mekonnen, Teferi; Meshkat, Mahboobeh; Mestrovic, Tomislav; Jonasson, Junmei Miao; Miazgowski, Tomasz; Michalek, Irmina Maria; Minh, Le Huu Nhat; Mini, G.K.; Miranda, J. Jaime; Mirfakhraie, Reza; Mirrakhimov, Erkin M.; Mirza-Aghazadeh-Attari, Mohammad; Misganaw, Awoke; Misgina, Kebede Haile; Mishra, Manish; Moazen, Babak; Mohamed, Nouh Saad; Mohammadi, Esmaeil; Mohammadi, Mohsen; Mohammadian-Hafshejani, Abdollah; Mohammadshahi, Marita; Mohseni, Alireza; Mojiri-Forushani, Hoda; Mokdad, Ali H.; Momtazmanesh, Sara; Monasta, Lorenzo; Moniruzzaman, Md; Mons, Ute; Montazeri, Fateme; Ghalibaf, AmirAli Moodi; Moradi, Yousef; Moradi, Maryam; Sarabi, Mostafa Moradi; Morovatdar, Negar; Morrison, Shane Douglas; Morze, Jakub; Mossialos, Elias; Mostafavi, Ebrahim; Mueller, Ulrich Otto; Mulita, Francesk; Mulita, Admir; Murillo-Zamora, Efren; Musa, Kamarul Imran; Mwita, Julius C.; Nagaraju, Shankar Prasad; Naghavi, Mohsen; Nainu, Firzan; Nair, Tapas Sadasivan; Najmuldeen, Hastyar Hama Rashid; Nangia, Vinay; Nargus, Shumaila; Naser, Abdallah Y.; Nassereldine, Hasan; Natto, Zuhair S.; Nauman, Javaid; Nayak, Biswa Prakash; Ndejjo, Rawlance; Negash, Hadush; Negoi, Ruxandra Irina; Nguyen, Hau Thi Hien; Nguyen, Dang H.; Nguyen, Phat Tuan; Nguyen, Van Thanh; Nguyen, Hien Quang; Niazi, Robina Khan; Nigatu, Yeshambel T.; Ningrum, Dina Nur Anggraini; Nizam, Muhammad A.; Nnyanzi, Lawrence Achilles; Noreen, Mamoona; Noubiap, Jean Jacques; Nzoputam, Ogochukwu Janet; Nzoputam, Chimezie Igwegbe; Oancea, Bogdan; Odogwu, Nkechi Martina; Odukoya, Oluwakemi Ololade; Ojha, Vivek Anand; Okati-Aliabad, Hassan; Okekunle, Akinkunmi Paul; Okonji, Osaretin Christabel; Okwute, Patrick Godwin; Olufadewa, Isaac Iyinoluwa; Onwujekwe, Obinna E.; Ordak, Michal; Ortiz, Alberto; Osuagwu, Uchechukwu Levi; Oulhaj, Abderrahim; Owolabi, Mayowa O.; Padron-Monedero, Alicia; Padubidri, Jagadish Rao; Palladino, Raffaele; Panagiotakos, Demosthenes; Panda-Jonas, Songhomitra; Pandey, Ashok; Pandey, Anamika; Pandi-Perumal, Seithikurippu R.; Stoian, Anca Mihaela Pantea; Pardhan, Shahina; Parekh, Tarang; Parekh, Utsav; Pasovic, Maja; Patel, Jay; Patel, Jenil R.; Paudel, Uttam; Pepito, Veincent Christian Filipino; Pereira, Marcos; Perico, Norberto; Perna, Simone; Petcu, Ionela-Roxana; Petermann-Rocha, Fanny Emily; Podder, Vivek; Postma, Maarten J.; Pourali, Ghazaleh; Pourtaheri, Naeimeh; Prates, Elton Junio Sady; Qadir, Mirza Muhammad Fahd; Qattea, Ibrahim; Raee, Pourya; Rafique, Ibrar; Rahimi, Mehran; Rahimifard, Mahban; Rahimi-Movaghar, Vafa; Rahman, Md Obaidur; Rahman, Muhammad Aziz; Rahman, Mohammad Hifz Ur; Rahman, Mosiur; Rahman, Md Mosfequr; Rahmani, Mohamed; Rahmani, Shayan; Rahmanian, Vahid; Rahmawaty, Setyaningrum; Rahnavard, Niloufar; Rajbhandari, Bibek; Ram, Pradhum; Ramazanu, Sheena; Rana, Juwel; Rancic, Nemanja; Ranjha, Muhammad Modassar Ali Nawaz; Rao, Chythra R.; Rapaka, Deepthi; Rasali, Drona Prakash; Rashedi, Sina; Rashedi, Vahid; Rashid, Ahmed Mustafa; Rashidi, Mohammad-Mahdi; Ratan, Zubair Ahmed; Rawaf, Salman; Rawal, Lal; Redwan, Elrashdy Moustafa Mohamed; Remuzzi, Giuseppe; Rengasamy, Kannan R. R.; Renzaho, Andre M. N.; Reyes, Luis Felipe; Rezaei, Nima; Rezaei, Nazila; Rezaeian, Mohsen; Rezazadeh, Hossein; Riahi, Seyed Mohammad; Rias, Yohanes Andy; Riaz, Muhammad; Ribeiro, Daniela; Rodrigues, Monica; Rodriguez, Jefferson Antonio Buendia; Roever, Leonardo; Rohloff, Peter; Roshandel, Gholamreza; Roustazadeh, Abazar; Rwegerera, Godfrey M.; Saad, Aly M. A.; Saber-Ayad, Maha Mohamed; Sabour, Siamak; Sabzmakan, Leila; Saddik, Basema; Sadeghi, Erfan; Saeed, Umar; Moghaddam, Sahar Saeedi; Safi, Sare; Safi, Sher Zaman; Saghazadeh, Amene; Sharif-Askari, Narjes Saheb; Sharif-Askari, Fatemeh Saheb; Sahebkar, Amirhossein; Sahoo, Soumya Swaroop; Sahoo, Harihar; Saif-Ur-Rahman, K.M.; Sajid, Mirza Rizwan; Salahi, Sarvenaz; Salahi, Saina; Saleh, Mohamed A.; Salehi, Mohammad Amin; Salomon, Joshua A.; Sanabria, Juan; Sanjeev, Rama Krishna; Sanmarchi, Francesco; Santric-Milicevic, Milena M.; Sarasmita, Made Ary; Sargazi, Saman; Sathian, Brijesh; Sathish, Thirunavukkarasu; Sawhney, Monika; Schlaich, Markus P.; Schmidt, Maria Ines; Schuermans, Art; Seidu, Abdul-Aziz; Kumar, Nachimuthu Senthil; Sepanlou, Sadaf G.; Sethi, Yashendra; Seylani, Allen; Shabany, Maryam; Shafaghat, Tahereh; Shafeghat, Melika; Shafie, Mahan; Shah, Nilay S.; Shahid, Samiah; Shaikh, Masood Ali; Shanawaz, Mohd; Shannawaz, Mohammed; Sharfaei, Sadaf; Shashamo, Bereket Beyene; Shiri, Rahman; Shittu, Aminu; Shivakumar, K.M.; Shivalli, Siddharudha; Shobeiri, Parnian; Shokri, Fereshteh; Shuval, Kerem; Sibhat, Migbar Mekonnen; Silva, Luis Manuel Lopes Rodrigues; Simpson, Colin R.; Singh, Jasvinder A.; Singh, Paramdeep; Singh, Surjit; Siraj, Md Shahjahan; Skryabina, Anna Aleksandrovna; Sohag, Abdullah Al Mamun; Soleimani, Hamidreza; Solikhah, Solikhah; Soltani-Zangbar, Mohammad Sadegh; Somayaji, Ranjani; Sorensen, Reed J. D.; Starodubova, Antonina V.; Sujata, Sujata; Suleman, Muhammad; Sun, Jing; Sundstr�m, Johan; Tabar�s-Seisdedos, Rafael; Tabatabaei, Seyyed Mohammad; Tabatabaeizadeh, Seyed-Amir; Tabish, Mohammad; Taheri, Majid; Taheri, Ensiyeh; Taki, Elahe; Tamuzi, Jacques J. L. Lukenze; Tan, Ker-Kan; Tat, Nathan Y.; Taye, Birhan Tsegaw; Temesgen, Worku Animaw; Temsah, Mohamad-Hani; Tesler, Riki; Thangaraju, Pugazhenthan; Thankappan, Kavumpurathu Raman; Thapa, Rajshree; Tharwat, Samar; Thomas, Nihal; Ticoalu, Jansje Henny Vera; Tiyuri, Amir; Tonelli, Marcello; Tovani-Palone, Marcos Roberto; Trico, Domenico; Trihandini, Indang; Tripathy, Jaya Prasad; Tromans, Samuel Joseph; Tsegay, Guesh Mebrahtom; Tualeka, Abdul Rohim; Tufa, Derara Girma; Tyrovolas, Stefanos; Ullah, Sana; Upadhyay, Era; Vahabi, Seyed Mohammad; Vaithinathan, Asokan Govindaraj; Valizadeh, Rohollah; van Daalen, Kim Robin; Vart, Priya; Varthya, Shoban Babu; Vasankari, Tommi Juhani; Vaziri, Siavash; Verma, Madhur Verma; Verras, Georgios-Ioannis; Vo, Danh Cao; Wagaye, Birhanu; Waheed, Yasir; Wang, Ziyue; Wang, Yanqing; Wang, Cong; Wang, Fang; Wassie, Gizachew Tadesse; Wei, Melissa Y. Wei; Weldemariam, Abrha Hailay; Westerman, Ronny; Wickramasinghe, Nuwan Darshana; Wu, YiFan; Wulandari, Ratna D. W. I.; Xia, Juan; Xiao, Hong; Xu, Suowen; Xu, Xiaoyue; Yada, Dereje Y.; Yang, Lin; Yatsuya, Hiroshi; Yesiltepe, Metin; Yi, Siyan; Yohannis, Hunachew Kibret; Yonemoto, Naohiro; You, Yuyi; Zaman, Sojib Bin; Zamora, Nelson; Zare, Iman; Zarea, Kourosh; Zarrintan, Armin; Zastrozhin, Mikhail Sergeevich; Zeru, Naod Gebrekrstos; Zhang, Zhi-Jiang; Zhong, Chenwen; Zhou, Jingjing; Zieli?ska, Magdalena; Zikarg, Yossef Teshome; Zodpey, Sanjay; Zoladl, Mohammad; Zou, Zhiyong; Zumla, Alimuddin; Zuniga, Yves Miel H.; Magliano, Dianna J.; Murray, Christopher J. L.; Hay, Simon I.; Vos, Theo
Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings: In 2021, there were 529 million (95% uncertainty interval [UI] 500�564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6�1% (5�8�6�5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9�3% [8�7�9�9]) and, at the regional level, in Oceania (12�3% [11�5�13�0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76�1% (73�1�79�5) in individuals aged 75�79 years. Total diabetes prevalence�especially among older adults�primarily reflects type 2 diabetes, which in 2021 accounted for 96�0% (95�1�96�8) of diabetes cases and 95�4% (94�9�95�9) of diabetes DALYs worldwide. In 2021, 52�2% (25�5�71�8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24�3% (18�5�30�4) worldwide between 1990 and 2021. By 2050, more than 1�31 billion (1�22�1�39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16�8% (16�1�17�6) in north Africa and the Middle East and 11�3% (10�8�11�9) in Latin America and Caribbean. By 2050, 89 (43�6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation: Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding: Bill & Melinda Gates Foundation. � 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: An experimental to clinical perspective
(Academic Press, 2022-09-06T00:00:00) Yadav, Poonam; Khurana, Amit; Bhatti, Jasvinder Singh; Weiskirchen, Ralf; Navik, Umashanker
Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting these risk factors is a rational option for inhibiting NASH progression. In addition, NASH could be treated with therapies that target the metabolic abnormalities causing disease pathogenesis (such as de novo lipogenesis and insulin resistance) as well with medications targeting downstream processes such as cellular damage, apoptosis, inflammation, and fibrosis. Glucagon-like peptide (GLP-1), is an incretin hormone dysregulated in both experimental and clinical NASH, which triggers many signaling pathways including fibroblast growth factor (FGF) that augments NASH pathogenesis. Growing evidence indicates that GLP-1 in concert with FGF-21 plays crucial roles in the conservation of glucose and lipid homeostasis in metabolic disorders. In line, GLP-1 stimulation improves hepatic ballooning, steatosis, and fibrosis in NASH. A recent clinical trial on NASH patients showed that the upregulation of FGF-21 decreases liver fibrosis and hepatic steatosis, thus improving the pathogenesis of NASH. Hence, therapeutic targeting of the GLP-1/FGF axis could be therapeutically beneficial for the remission of NASH. This review outlines the significance of the GLP-1/FGF-21 axis in experimental and clinical NASH and highlights the activity of modulators targeting this axis as potential salutary agents for the treatment of NASH. � 2022 Elsevier Ltd
Gut microbiota dysbiosis and Huntington's disease: Exploring the gut-brain axis and novel microbiota-based interventions
(Elsevier Inc., 2023-06-24T00:00:00) Sharma, Garvita; Biswas, Shristi Saroj; Mishra, Jayapriya; Navik, Umashanker; Kandimalla, Ramesh; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches. � 2023 Elsevier Inc.
Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies
(Baishideng Publishing Group Inc, 2023-04-12T00:00:00) Khullar, Naina; Bhatti, Jasvinder Singh; Singh, Satwinder; Thukral, Bhawana; Hemachandra Reddy, P.; Bhatti, Gurjit Kaur
As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19. � The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Lifestyle modifications and nutrition in Alzheimer's disease
(Elsevier, 2023-06-16T00:00:00) Bhatti, Gurjit Kaur; Mishra, Jayapriya; Sehrawat, Abhishek; Sharma, Eva; Kanozia, Rubal; Navik, Umashanker; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
Alzheimer's disease (AD) is a progressive chronic neurodegenerative disorder that is increasingly seen in developed and developing countries that subjugate older people. The exacerbation begins with the disease seen with the symptoms like deterioration of mental ability, memory, and cognitive deficits, which ultimately decline the physical activity also, and the severity of this disease causes the death of the patient. There is no proper medication and cure available to date, which can precisely prevent the condition efficiently. But it is essential to diagnose it before its destructive phase and consult for necessary treatments and procedures taken by the patient and the caregivers. Apart from clinical trials, the first and foremost thing is to focus on lifestyle; a way of living can have a more significant impact on a person's health. One can stay healthy for a longer time or fight against the disease by developing strategies like boosting immunity and staying physically fit enough, or else, one can successfully delay the appearance of disease with strong immunity and a healthier lifestyle. And the other promising fact is taking nutritious food, which is helpful to build a robust internal defense system against the diseased condition and lowering the risk of ailments. This chapter will focus on the pathophysiology of Alzheimer's disease, lifestyle modifications, and nutritional interventions in AD. � 2023 Elsevier Inc. All rights reserved.
Methionine as a double-edged sword in health and disease: Current perspective and future challenges
(Elsevier Ireland Ltd, 2021-10-25T00:00:00) Navik, Umashanker; Sheth, Vaibhav G.; Khurana, Amit; Jawalekar, Snehal Sainath; Allawadhi, Prince; Gaddam, Ravinder Reddy; Bhatti, Jasvinder Singh; Tikoo, Kulbhushan
Methionine is one of the essential amino acids and plays a vital role in various cellular processes. Reports advocate that methionine restriction and supplementation provide promising outcomes, and its regulation is critical for maintaining a healthy life. Dietary methionine restriction in houseflies and rodents has been proven to extend lifespan. Contrary to these findings, long-term dietary restriction of methionine leads to adverse events such as bone-related disorders, stunted growth, and hyperhomocysteinemia. Conversely, dietary supplementation of methionine improves hepatic steatosis, insulin resistance, inflammation, fibrosis, and bone health. However, a high level of methionine intake shows adverse effects such as hyperhomocysteinemia, reduced body weight, and increased cholesterol levels. Therefore, dietary methionine in a safe dose could have medicinal values. Hence, this review is aimed to provide a snapshot of the dietary role and regulation of methionine in the modulation of health and age-related diseases. � 2021 Elsevier B.V.
Microbiome in Pulmonary Tuberculosis
(Springer Nature, 2022-03-25T00:00:00) Rakshit, Arnab; Verma, Aarti; Verma, Saloni; Bhatti, Gurjit Kaur; Khurana, Amit; Bhatti, Jasvinder Singh; Jawalekar, Snehal Sainath; Navik, Umashanker
Tuberculosis (TB) is among the global dominant fatal infection caused by a single organism, and it is still holding its position in spite of the golden age of the antibiotics. The recent studies are mostly focused on finding the prevention of TB rather than curing it because the antimycobacterial chemotherapy is failing constantly due to emerging multidrug resistance (MDR). Further, the intestinal microbiota is the central command for maintaining the homeostasis of the microbial profile of different organs. The change in the intestinal microbiota effects homeostasis by impacting the immune response to the microbial profile of various organs. Thus, it also affects the chance of contracting the infections. Here in this chapter, it is mostly focused on the reason behind the TB getting chance to infect the healthy lung tissue. It is also found that dysbiosis in gut microbiota, which directly affects the lung, plays a key role in giving TB a chance to hold its ground. It also highlights the new curative method which we can apply by correcting the gut microbial profile, which in turn corrects the lung microbial profile and rest of the function will done by body�s own immune system. It is thus found that proper restoration of the microbial profile enhances the immune response and could restore the homeostasis. � The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2022.
Mitochondria-Targeted Small Peptide, SS31 Ameliorates Diabetes Induced Mitochondrial Dynamics in Male TallyHO/JngJ Mice
(Springer, 2020-10-07T00:00:00) Bhatti, Jasvinder Singh; Thamarai, Kavya; Kandimalla, Ramesh; Manczak, Maria; Yin, Xiangling; Kumar, Subodh; Vijayan, Murali; Reddy, P. Hemachandra
The escalating burden of type 2 diabetes (T2D) and its related complications has become a major public health challenge worldwide. Substantial evidence indicates that T2D is one of the culprits for the high prevalence of Alzheimer�s disease (AD) in diabetic subjects. This study aimed to investigate the possible mitochondrial alterations in the pancreas induced by hyperglycemia in diabetes. We used a diabetic TallyHO/JngJ (TH) and non-diabetic, SWR/J mice strains. The diabetic and non-diabetic status in animals was assessed by performing intraperitoneal glucose tolerance test at four time points, i.e., 4, 8, 16, and 24�weeks of age. We divided 24-week-old TH and SWR/J mice into 3 groups: controls, diabetic TH mice, and diabetic TH mice treated with SS31 peptide. After the treatment of male TH mice with SS31, intraperitoneally, for 4�weeks, we studied mitochondrial dynamics, biogenesis, and function. The mRNA and protein expression levels of mitochondrial proteins were evaluated using qPCR and immunoblot analysis. The diabetic mice after 24�weeks of age showed overt pancreatic injury as demonstrated by disintegration and atrophy of ? cells with vacuolization and reduced islet size. Mitochondrial dysfunction was observed in TH mice, as evidenced by significantly elevated H2O2 production, lipid peroxidation, and reduced ATP production. Furthermore, mRNA expression and immunoblot analysis of mitochondrial dynamics genes were significantly affected in diabetic mice, compared with controls. However, treatment of animals with SS31 reduced mitochondrial dysfunction and restored most of the mitochondrial functions and mitochondrial dynamics processes to near normal in TH mice. In conclusion, mitochondrial dysfunction is established as one of the molecular events that occur in the pathophysiology of T2D. Further, SS31 treatment may confer protection against the mitochondrial alterations induced by hyperglycemia in diabetic TallyHO/JngJ mice. � 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens
(Elsevier Ireland Ltd, 2023-02-11T00:00:00) Bhatti, Jasvinder Singh; Khullar, Naina; Vijayvergiya, Rajesh; Navik, Umashanker; Bhatti, Gurjit Kaur; Reddy, P. Hemachandra
Aging bears many hard knocks, but heart disorders earn a particular allusion, being the most widespread. Cardiovascular diseases (CVDs) are becoming the biggest concern to mankind due to sundry health conditions directly or indirectly related to heart-linked abnormalities. Scientists know that mitochondria play a critical role in the pathophysiology of cardiac diseases. Both environment and genetics play an essential role in modulating and controlling mitochondrial functions. Even a minor abnormality may prove detrimental to heart function. Advanced age combined with an unhealthy lifestyle can cause most cardiomyocytes to be replaced by fibrotic tissue which upsets the conducting system and leads to arrhythmias. An aging heart encounters far more heart-associated comorbidities than a young heart. Many state-of-the-art technologies and procedures are already being used to prevent and treat heart attacks worldwide. However, it remains a mystery when this heart bomb would explode because it lacks an alarm. This calls for a novel and effective strategy for timely diagnosis and a sure-fire treatment. This review article provides a comprehensive overture of prospective potentials of mitochondrial miRNAs that predict complicated and interconnected pathways concerning heart ailments and signature compilations of relevant miRNAs as biomarkers to plot the role of miRNAs in epigenomics. This article suggests that analysis of DNA methylation patterns in age-associated heart diseases may determine age-impelled biomarkers of heart disease. � 2023 Elsevier B.V.
Modulating autophagy and mitophagy as a promising therapeutic approach in neurodegenerative disorders
(Elsevier Inc., 2022-11-04T00:00:00) Mishra, Jayapriya; Bhatti, Gurjit Kaur; Sehrawat, Abhishek; Singh, Charan; Singh, Arti; Reddy, Arubala P.; Reddy, P. Hemachandra; Bhatti, Jasvinder Singh
The high prevalence of neurodegenerative diseases has become a major public health challenge and is associated with a tremendous burden on individuals, society and federal governments worldwide. Protein misfolding and aggregation are the major pathological hallmarks of several neurodegenerative disorders. The cells have evolved several regulatory mechanisms to deal with aberrant protein folding, namely the classical ubiquitin pathway, where ubiquitination of protein aggregates marks their degradation via lysosome and the novel autophagy or mitophagy pathways. Autophagy is a catabolic process in eukaryotic cells that allows the lysosome to recycle the cell's own contents, such as organelles and proteins, known as autophagic cargo. Their most significant role is to keep cells alive in distressed situations. Mitophagy is also crucial for reducing abnormal protein aggregation and increasing organelle clearance and partly accounts for maintaining cellular homeostasis. Furthermore, substantial data indicate that any disruption in these homeostatic mechanisms leads to the emergence of several age-associated metabolic and neurodegenerative diseases. So, targeting autophagy and mitophagy might be a potential therapeutic strategy for a variety of health conditions. � 2022