-
1.
Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology.
Kango, G, Malek, R, Mannuel, H, Hussain, A
Current opinion in oncology. 2024;(3):195-201
Abstract
PURPOSE OF REVIEW Targeting specific steroidogenic enzymes is effective in decreasing testosterone synthesis, resulting in significant antitumor effects in prostate cancer. Such treatments result in disruptions of complicated and intertwining pathways with systemic physiologic consequences via effects on the adrenal gland and renin-angiotensin-aldosterone axis. This review highlights some of these aspects that need to be taken into consideration when treating patients with androgen biosynthesis inhibitors. RECENT FINDINGS Targeting CYP17A1, a key enzyme involved in androgen biosynthesis, is a well established treatment in prostate cancer. More recently, efforts are underway to target a gatekeeper enzyme of steroidogenesis, CYP11A1. This enzyme mediates conversion of cholesterol to pregnenolone, the first step in steroid hormone biogenesis. Studies are beginning to demonstrate antitumor effects of ODM-208, a CYP11A1 inhibitor in prostate cancer. Although anticipated to have a therapeutic role in prostate cancer, there are potential downstream effects of CYP11A1 targeting arising from suppression of the entire adrenal cortex, including long-term adrenal insufficiency and possibly cardiovascular dysregulation. SUMMARY Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.
-
2.
Cross Talk Between Cells and the Current Bioceramics in Bone Regeneration: A Comprehensive Review.
Khayatan, D, Bagherzadeh Oskouei, A, Alam, M, Mohammadikhah, M, Badkoobeh, A, Golkar, M, Abbasi, K, Karami, S, Sayyad Soufdoost, R, Kamali Hakim, L, et al
Cell transplantation. 2024;:9636897241236030
Abstract
The conventional approach for addressing bone defects and stubborn non-unions typically involves the use of autogenous bone grafts. Nevertheless, obtaining these grafts can be challenging, and the procedure can lead to significant morbidity. Three primary treatment strategies for managing bone defects and non-unions prove resistant to conventional treatments: synthetic bone graft substitutes (BGS), a combination of BGS with bioactive molecules, and the use of BGS in conjunction with stem cells. In the realm of synthetic BGS, a multitude of biomaterials have emerged for creating scaffolds in bone tissue engineering (TE). These materials encompass biometals like titanium, iron, magnesium, and zinc, as well as bioceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP). Bone TE scaffolds serve as temporary implants, fostering tissue ingrowth and the regeneration of new bone. They are meticulously designed to enhance bone healing by optimizing geometric, mechanical, and biological properties. These scaffolds undergo continual remodeling facilitated by bone cells like osteoblasts and osteoclasts. Through various signaling pathways, stem cells and bone cells work together to regulate bone regeneration when a portion of bone is damaged or deformed. By targeting signaling pathways, bone TE can improve bone defects through effective therapies. This review provided insights into the interplay between cells and the current state of bioceramics in the context of bone regeneration.
-
3.
Impact of COVID-19 on risks and deaths of non-communicable diseases in the Western Pacific region.
Xu, X, Shi, Z, Zhou, L, Lin, J, Atlantis, E, Chen, X, Hussain, A, Wang, Y, Wang, Y
The Lancet regional health. Western Pacific. 2024;:100795
Abstract
Countries and areas in the Western Pacific region (WPR) experienced the COVID-19 pandemic and took various preventive measures, which affected non-communicable diseases (NCDs) risks and mortality. Due to differences in COVID-19 prevention measures and other characteristics such as culture, religions, political systems, socioeconomic development, lifestyles, and health care systems, the effects of COVID-19 on NCDs varied greatly among WPR countries. Most countries had an increased all-cause and NCDs mortality during the pandemic, but some developed countries, including New Zealand, Singapore and Australia reported decreased mortality. The pandemic and the preventive measures increased NCD risk factors including unhealthy diet, lack of physical activity and sleep disorders. The effects varied by socioeconomic status and health conditions. COVID-19 related stress, food shortages, and confined lifestyle had immediate detrimental effects on NCDs, and also affected pregnancy outcomes with long-term effects on NCDs risks in coming years.
-
4.
Oxygen and Iron Availability Shapes Metabolic Adaptations of Cancer Cells.
Wang, R, Hussain, A, Guo, QQ, Jin, XW, Wang, MM
World journal of oncology. 2024;(1):28-37
Abstract
The dynamic changes between glycolysis and oxidative phosphorylation (OXPHOS) for adenosine triphosphate (ATP) output, along with glucose, glutamine, and fatty acid utilization, etc., lead to the maintenance and selection of growth advantageous to tumor cell subgroups in an environment of iron starvation and hypoxia. Iron plays an important role in the three major biochemical reactions in nature: photosynthesis, nitrogen fixation, and oxidative respiration, which all require the participation of iron-sulfur proteins, such as ferredoxin, cytochrome b, and the complex I, II, III in the electron transport chain, respectively. Abnormal iron-sulfur cluster synthesis process or hypoxia will directly affect the function of mitochondrial electron transfer and mitochondrial OXPHOS. More research results have indicated that iron metabolism, oxygen availability and hypoxia-inducible factor mutually regulate the shift between glycolysis and OXPHOS. In this article, we make a perspective review to provide novel opinions of the regulation of glycolysis and OXPHOS in tumor cells.
-
5.
Navigating the Gut-Cardiac Axis: Understanding Cardiovascular Complications in Inflammatory Bowel Disease.
Sinha, T, Zain, Z, Bokhari, SFH, Waheed, S, Reza, T, Eze-Odurukwe, A, Patel, M, Almadhoun, MKIK, Hussain, A, Reyaz, I
Cureus. 2024;(2):e55268
Abstract
Inflammatory bowel disease (IBD) presents a complex interplay of chronic inflammation in the gastrointestinal tract and is associated with various extraintestinal manifestations, including cardiovascular complications (CVCs). IBD patients face an elevated risk of CVCs, including coronary artery disease, heart failure, arrhythmias, stroke, peripheral artery disease, venous thromboembolism, and mesenteric ischemia, necessitating comprehensive cardiovascular risk assessment and management. The intricate interplay between chronic inflammation, genetic predisposition, environmental factors, and immune dysregulation likely contributes to the development of CVCs in IBD patients. While the exact mechanisms linking IBD and CVCs remain speculative, potential pathways may involve shared inflammatory pathways, endothelial dysfunction, dysbiosis of the gut microbiome, and traditional cardiovascular risk factors exacerbated by the chronic inflammatory state. Moreover, IBD medications, particularly corticosteroids, may impact cardiovascular health by inducing hypertension, insulin resistance, and dyslipidemia, further amplifying the overall CVC risk. Lifestyle factors such as smoking, obesity, and dietary habits may also exacerbate cardiovascular risks in individuals with IBD. Lifestyle modifications, including smoking cessation, adoption of a heart-healthy diet, regular exercise, and optimization of traditional cardiovascular risk factors, play a fundamental role in mitigating CVC risk. Emerging preventive strategies targeting inflammation modulation and gut microbiome interventions hold promise for future interventions, although further research is warranted to elucidate their efficacy and safety profiles in the context of IBD. Continued interdisciplinary collaboration, advanced research methodologies, and innovative interventions are essential to address the growing burden of CVCs in individuals living with IBD and to improve their long-term cardiovascular outcomes.
-
6.
Identification of High-Affinity Inhibitors of TANK-Binding Kinase 1 (TBK1): A Promising Frontier for Controlling Inflammatory Signaling in Cancer.
Jairajpuri, DS, Mohammad, T, Hussain, A, Alajmi, MF, Yadav, DK, Hassan, MI
Discovery medicine. 2024;(180):129-139
Abstract
BACKGROUND TANK-binding kinase 1 (TBK1) is an important serine/threonine kinase involved in inflammatory signaling pathways, influencing cellular processes such as proliferation, programmed cell death, autophagy, and immune response regulation. Dysregulation of TBK1 has been linked to cancer progression and neurodegenerative disorders, making it an attractive target for therapeutic development. This study aimed to identify potential TBK1 inhibitors using a structure-based virtual screening approach. METHODS We conducted a comprehensive screening of the ZINC database to identify compounds with high binding affinity for TBK1, employing molecular docking as the primary selection criterion. The top candidates were then subjected to extensive 200 ns molecular dynamics (MD) simulations to assess the conformational dynamics of TBK1 and the stability of the protein-ligand complexes, with a focus on ZINC02095133 and ZINC02130647. RESULTS The findings revealed that TBK1 forms stable complexes with ZINC02095133 and ZINC02130647, demonstrating consistent interactions throughout the MD simulations. This suggests that these compounds hold promise as potential lead molecules for future therapies targeting TBK1. CONCLUSIONS This study identifies ZINC02095133 and ZINC02130647 as promising TBK1 inhibitors with therapeutic potential. However, further experimental validation and optimization are required to develop novel inhibitors for diseased conditions associated with TBK1 signaling. These findings pave the way for future investigations into the clinical utility of these compounds in combating TBK1-related pathologies.
-
7.
Hazardous or Advantageous: Uncovering the Roles of Heavy Metals and Humic Substances in Shilajit (Phyto-mineral) with Emphasis on Heavy Metals Toxicity and Their Detoxification Mechanisms.
Hussain, A, Saeed, A
Biological trace element research. 2024
Abstract
Shilajit is a phyto-mineral diffusion and semi-solid matter used as traditional medicine with extraordinary health benefits. This study provides a comprehensive data on Shilajit with emphasis on heavy metal profile, associated toxicities, and metal detoxification mechanisms by humic substances present in Shilajit. Data was searched across papers and traditional books using Google Scholar, PubMed, Science Direct, Medline, SciELO, Web of Science, and Scopus as key scientific databases. Findings showed that Shilajit is distributed in almost 20 regions of the world with uses against 20 health problems as traditional medicine. With various humic substances, almost 11 biological activities were reported in Shilajit. This phyto-mineral diffusion possesses around 65 heavy metals including the toxic heavy metals like Cu, Al, Pb, As, Cd, and Hg. However, humic substances in Shilajit actively detoxify around 12 heavy metals. The recommended levels of heavy metals by WHO and FDA in herbal drugs is 0.20 and 0.30 ppm for Cd, 1 ppm for Hg, 10.00 ppm for As and Pb, 20 ppm for Cu, and 50 ppm for Zn. The levels of reported metals in Shilajit were found to be lower than the permissible limits set by WHO and FDA, except in few studies where exceeded levels were reported. Shilajit consumption without knowing permissible levels of metals is not safe and could pose serious health problems. Although the humic substances and few metals in Shilajit are beneficial in terms of chelating toxic heavy metals, the data on metal detoxification still needs to be clarified.
-
8.
Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights.
Sharifa, M, Ghosh, T, Daher, OA, Bhusal, P, Alaameri, YA, Naz, J, Ekhator, C, Bellegarde, SB, Bisharat, P, Vaghani, V, et al
Cureus. 2023;(10):e47058
Abstract
This comprehensive review delves into the intricate relationship between the gut microbiota and multiple sclerosis (MS), shedding light on the potential therapeutic avenues for this complex autoimmune disease. It emphasizes the multifactorial nature of MS, including genetic, environmental, and gender-related factors. Furthermore, the article highlights the emerging role of gut microbiota in MS pathophysiology, particularly in terms of gut dysbiosis, oxidative stress, and inflammasome activation within the gut-brain axis. This interplay raises intriguing questions about how the gut microbiota influences the onset and progression of MS. Environmental factors, such as diet and pollutants, add further layers of complexity to the connection between gut health and MS risk. This review also discusses promising therapeutic interventions, such as fecal microbiota transplantation, probiotics, dietary adjustments, and gut-derived metabolites that offer potential avenues for managing MS. It underscores the need for ongoing research to fully unravel the complexities of the role of the gut-brain axis in MS. Ultimately, this article provides a comprehensive exploration of the topic, offering hope for novel preventive and therapeutic strategies that could significantly improve the lives of individuals affected by this challenging autoimmune condition.
-
9.
The Benefits Outweigh the Risks of Treating Hypercholesterolemia: The Statin Dilemma.
Hussain, A, Kaler, J, Ray, SD
Cureus. 2023;(1):e33648
Abstract
Cardiovascular diseases are one of the leading causes of death in the United States; therefore, primary and secondary prevention are of the utmost importance. In this regard, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) reductase inhibitors, also known as statins, have been anointed as the primary treatment method for lowering cholesterol to prevent cardiovascular diseases. Statins decrease the low-density lipoprotein (LDL) cholesterol and triglycerides in the body, thus lowering the total body cholesterol levels. Despite the benefits associated with statins, it is essential to understand the adverse effects of these drugs. Myotoxicity and statin-associated muscle symptoms are the most common adverse effects of statins. The impairment of mitochondrial function is another adverse effect that can lead to hepatic dysfunction, neurocognitive effects, and potentially the new onset of diabetes. The exact pathophysiology of these side effects is still not fully understood. However, several mechanisms have been proposed, although there is significant overlap among the hypothetical propositions. Understanding the overall outcomes of each of these adverse effects can allow a healthcare practitioner to carefully map out whether statin administration should be used to prevent hypercholesterolemia in the body. The adverse effect of statins is dependent on both the dose and the type of statin used. Lipophilic statins tend to possess a more remarkable ability to infiltrate membranes; they have been hypothesized to cause statin-induced myopathies as well as neurocognitive effects by significantly crossing the blood-brain barrier. In summary, this review has focused on the mechanistic and clinical aspects of this statin class of medication. Proposed mechanisms for different adverse effects associated with statins remain a focus of this communication.
-
10.
Effect of lifestyle intervention on HbA1c levels in overweight and obese adults with type 2 diabetes across ethnicities: A systematic review and meta-analysis of randomized controlled trials.
Yang, J, Xia, Y, Sun, Y, Guo, Y, Shi, Z, Cristina do Vale Moreira, N, Zuo, H, Hussain, A
Diabetes research and clinical practice. 2023;199:110662
-
-
-
Free full text
Plain language summary
Weight loss can benefit overweight and obese patients with type 2 diabetes mellitus (T2DM) with regards to cardiovascular risk factors, including glycaemic control. This systematic review and meta-analysis of 30 randomised controlled trials, including 7850 patients, aimed to evaluate racial/ethnic differences in response to lifestyle interventions for weight loss on glycosylated haemoglobin (HbA1c, a measure of glycaemic control) in overweight or obese patients with T2DM. Lifestyle interventions were associated with statistically significant reductions in HbA1c in White and Asian, but not in Black/African or Hispanic populations, although the latter were based on only 2 and 3 small trials, respectively, and may have therefore lacked statistical power. Reductions in HbA1c were seen in studies which led to a weight loss of more than 5% as well as those less than 5%, with greater reductions being seen in the former group. The authors conclude that ethnic differences should be taken into account when considering lifestyle interventions for diabetes management.
Abstract
AIMS: Weight reduction is fundamental for the management and remission of diabetes. We aimed to assess ethnic differences in the effects of lifestyle weight-loss interventions on HbA1c levels in overweight or obese adults with type 2 diabetes mellitus (T2DM). METHODS We systematically searched PubMed/MEDLINE and Web of Science online databases up to 31 Dec 2022. Randomized controlled trials using lifestyle weight-loss interventions in overweight or obese adults with T2DM were selected. We performed subgroup analyses to explore the heterogeneity across different ethnicities (Asians, White/Caucasians, Black/Africans and Hispanics). A random effects model was applied to calculate weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS Thirty studies including 7580 subjects from different ethnicities were identified according to the predefined inclusion and exclusion criteria. HbA1c levels were significantly reduced by lifestyle weight-loss intervention. Notably, a significantly beneficial effect on HbA1c was observed in White/Caucasians (WMD = -0.59, 95% CI: -0.90, -0.28, P < 0.001) and Asians (WMD = -0.48, 95% CI: -0.63, -0.33, P < 0.001), but not in the Black/African or Hispanic group (both P > 0.05). The findings remained essentially unchanged in the sensitivity analysis. CONCLUSIONS Lifestyle weight-loss interventions had distinct beneficial effects on HbA1c levels in different ethnic groups with T2DM, especially in Caucasians and Asians.