Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways.

Lung cancer, characterized by its heterogeneity, presents a significant challenge in therapeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumor's ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article explores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. This review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small-cell lung cancer and small-cell lung cancer, underlining the need for subtype-specific treatments. Key signaling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. This review article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. This review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.

Increased susceptibility for nonsyndromic cleft lip with or without cleft palate by SLC19A1 80G>A genetic variation.

BACKGROUND: The disruption of craniofacial developmental pathways during early embryogenesis can lead to conditions such as nonsyndromic cleft lip with or without cleft palate (NSCL/P). Several lines of evidence indicate that inadequate maternal nutrition causes low folate levels during the periconceptional period, resulting in NSCL/P. Although substantial research has been conducted on the possible link between SLC19A1 genetic variants and NSCL/P, the association between SLC19A1 80G>A (rs1051266) and NSCL/P remains unclear. In the present study, the associations of SLC19A1 80G>A with NSCL/P risk were assessed by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs) by meta-analyses. METHODS: Following the PRISMA guidelines, a meta-analysis was conducted on 10 studies assessing the NSCL/P risk associated with SLC19A1 80G>A variant. To ascertain the degree of relationship between the SLC19A1 80G>A genetic variant and the risk of NSCL/P, data were analyzed in allelic, recessive and dominant genetic models. CI of OR for each study and the pooled data were obtained. All statistical analyses were conducted utilizing the MetaGenyo software tool, which integrates the adjustment of P values for multiple testing through the Bonferroni method. RESULTS: The pooled analysis showed that SLC19A1 80G>A variant significantly increased the NSCL/P risk in the allelic model (OR 1.39; 95% CI 1.00-1.92), recessive model (OR 1.37; 95% CI 1.03-1.82) and dominant models (OR 1.7; 95% CI 1.05-2.90). Publication bias was not observed. CONCLUSIONS: This study supports that the SLC19A1 80G>A genetic variant is associated with NSCL/P risk.

A Comprehensive Review of Cancer Drug-Induced Cardiotoxicity in Blood Cancer Patients: Current Perspectives and Therapeutic Strategies.

OPINION STATEMENT: Cardiotoxicity has emerged as a serious outcome catalyzed by various therapeutic targets in the field of cancer treatment, which includes chemotherapy, radiation, and targeted therapies. The growing significance of cancer drug-induced cardiotoxicity (CDIC) and radiation-induced cardiotoxicity (CRIC) necessitates immediate attention. This article intricately unveils how cancer treatments cause cardiotoxicity, which is exacerbated by patient-specific risks. In particular, drugs like anthracyclines, alkylating agents, and tyrosine kinase inhibitors pose a risk, along with factors such as hypertension and diabetes. Mechanistic insights into oxidative stress and topoisomerase-II-B inhibition are crucial, while cardiac biomarkers show early damage. Timely intervention and prompt treatment, especially with specific agents like dexrazoxane and beta-blockers, are pivotal in the proactive management of CDIC.

Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review.

Esophageal cancer is a highly aggressive and deadly disease, ranking as the sixth leading cause of cancer-related deaths worldwide. Despite advances in treatment, the prognosis remains poor. A multidisciplinary approach is crucial for achieving complete remission, with treatment options varying based on disease stage. Surgical intervention and endoscopic treatment are used for localized cancer, while systemic treatments like chemoradiotherapy and targeted drug therapy play a crucial role. Molecular markers such as HER2 and EGFR can be targeted with drugs like trastuzumab and cetuximab, and immunotherapy drugs like pembrolizumab and nivolumab show promise by targeting immune checkpoint proteins. Epigenetic modifications offer new avenues for targeted therapy. Treatment selection depends on factors like stage, tumor location, and patient health, with post-operative and rehabilitation care being essential. Early diagnosis, appropriate treatment, and supportive care are key to improving outcomes. Continued research is needed to develop effective targeted drugs with minimal side effects. This review serves as a valuable resource for clinicians and researchers dedicated to enhancing esophageal cancer treatment outcomes.

Neurological infection and complications of SARS-CoV-2: A review.

The primary target of severe acute respiratory syndrome coronavirus 2 is the respiratory system including the nose and lungs, however, it can also damage the kidneys, cardiovascular system and gastrointestinal system. Many recent reports suggested that severe acute respiratory syndrome coronavirus 2 infections can also affect the central nervous system as well as peripheral nervous system that lead to the several neurological complications. The virus can break the blood brain barrier and enters the brain via haematological route or directly by the angiotensin-converting enzyme 2 receptors present on endothelial cells of many cerebral tissues. The neurological complications are manifested by headache, dizziness, encephalopathy, encephalitis, cerebrovascular disease, anosmia, hypogeusia, muscle damage, etc. This review article described the possible routes and mechanism of nervous system infection and the range of neurological complications of COVID-19 that may help the medical practitioners and researchers to improve the clinical treatment and reduce the mortality rate among patients with viral diseases.

COVID-19 vaccination does not affect male sexual functions.

BACKGROUND: COVID-19 infection has been linked with erectile dysfunction, which has also raised apprehensions about the impact of COVID-19 vaccination on male sexual functions. The purpose of this study was to investigate the impact of COVID-19 vaccination on male sexual functions, such as erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. METHODS: We used International Index of Erectile Function (IIEF) questionnaire for data collection. Mixed methods were adopted for this study, which consisted of Google online form distribution and the distribution of hard copies of the form to those who were not internet friendly. All data were entered in a spreadsheet and scores were assigned to each response according to the standard scores given in the IIEF questionnaire. Fifteen questions, one corresponding to each question in the IIEF questionnaire, were included to assess the impact of COVID-19 vaccination on each sexual function. RESULTS: In the first part of analysis, we calculated sexual function scores and men reporting low sexual function scores (~ 15%) were excluded, providing us with 465 individuals for further analysis. Regarding the impact of COVID-19 vaccination on male sexual functions, 71% individuals reported no impact, 3% reported a decline, 2.7% reported an improvement, and 23.3% could not assess the impact. We also performed analysis on the basis of age-groups of the participants and the duration after vaccination, finding that there was no impact irrespective of the age of subjects or the length of period after vaccination. CONCLUSIONS: COVID-19 vaccination does not affect male sexual functions, including erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction.

IL-18 Gene Promoter Polymorphisms are Involved in Periodontal Disease: A Meta-Analysis.

Microbial plaque that builds up in the gingival crevice area causes inflammation and leads to periodontal disease. Previous research has shown an association between interleukins with periodontitis. The association between interleukin-18 (IL-18) gene polymorphism and periodontitis risk was studied extensively, but the results are contradictory. The aim of this study is to find the association of two IL-18 promoter variants namely -607 C > A (rs1946518) and -137 G > C (rs187238), and the risk of chronic and aggressive periodontal disease by meta-analysis. The databases of PubMed, Medline, Web of Science, and Google Scholar were all explored to find the appropriate studies. The MetaGenyo software was used to calculate each analysis. Outcomes of the pooled analyses revealed significantly elevated risk for periodontitis for both polymorphisms. There is no significant heterogeneity between studies. No significant publication bias was observed. This meta-analysis provided the evidence of a link between IL-18 gene polymorphism in periodontitis.

Role of CD4+ T Cells in Parkinson's Disease.

Parkinson's disease (PD) is a progressive condition that affects both the central nervous system and other body parts that are controlled by the nervous system. PD is characterized by brain dopaminergic neurons loss and, at present, there are only symptomatic treatments available to alleviate the effects of the disease. With extensive research, new insights have led to defining PD as a multi-system disorder with immune dysfunction playing a dominant part in the disease pathogenesis as well as its progression. Neuroinflammation in PD leads to neurodegeneration, which is, in turn, regulated by the peripheral adaptive immunity, with CD4+ T cells being a significant player. Patients with PD have diverse CD4+ T cell phenotypes and functional profiles. These phenotypes vary, from being proinflammatory (Th1 and Th17) to anti-inflammatory (Th2 and Tregs). This report focuses on reviewing the expression of CD4+ T cells in PD and its role in the prognosis and treatment of PD.

Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis.

INTRODUCTION: Non-syndromic cleft lip and palate (NSCLP) is one of the most common and challenging congenital deformities worldwide. Previous research has linked the methylenetetrahydrofolate dehydrogenase1 (MTHFD1) gene to orofacial cleft (OFC) susceptibility via a complex metabolism. Studies analyzing the MTHFD1 1958G > A variant and NSCLP are contradictory. This study aims to evaluate the association between the MTHFD1 1958G > A variant and NSCLP by meta-analysis. METHODS: PubMed, Web of Science, MEDLINE, and Google Scholar databases were searched to retrieve the eligible studies. A fixed- or random-effect model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). All analyses were calculated by Metagenyo software. To detect heterogeneity, the Cochrane Q and I2 statistics were used. The publication bias was estimated using funnel plots and Egger's test. RESULTS: Our study suggested that the MTHFD1 1958G > A variant allele "A" does not appear to increase the risk of NSCLP (A vs G random effect model: Overall P = .501, OR = 1.07, CI = 0.88-1.31; Asians P = .245, OR = 1.29, CI = 0.84-1.97; Caucasians P = .658, OR = 0.95, CI = 0.76-1.19). Similarly, mutant genotypes also did not exhibit increased risk for NSCLP in the overall populations as well in subgroup analysis by ethnicity (AA + AG vs GG: Overall P = .684, OR = 1.06, CI = 0.80-1.39; Asians P = .240, OR = 1.47, CI = 0.77-2.78; Caucasians P = .923, OR = 0.99, CI = 0.85-1.16). CONCLUSIONS: Our data suggest no association between the MTHFD1 1958G > A variant and NSCLP. Additional well-designed studies are needed to better understand the role of MTHFD1 polymorphisms in the etiopathogenesis of NSCLP.

Meta-Analysis on the Association of Neuropeptide Y rs16139 Variant With the Risk of Alcoholism.

Introduction: The neuropeptide-Y (NPY) is involved in the development of alcoholism through NPY receptors. A T>C mutation causes substitution of leucine to proline at codon 7 (L7P; rs16139) in the signal peptide of neuropeptide Y is known to cause a 42% increase in plasma NPY levels. Studies that analyzed the association between NPY rs16139 and alcoholism risk did not demonstrate conclusive evidence for this relationship. The present study aims to evaluate the association between NPY gene rs16139 variant and alcohol dependence. Method: An electronic search of databases including PubMed and Google Scholar was performed to retrieve studies investigating the association between NPY rs16139 and alcoholism. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in allelic and dominant genetic models. Sensitivity analyses and publication bias were assessed in our meta-analysis. The meta-analysis was conducted using the MetaGenyo web tool. Result: Significant heterogeneity was observed across studies (p < 0.001). Our results have shown that there is no significant association between NPY rs16139 variant and the risk of alcoholism in allelic (OR = 0.98, 95% CI 0.70-1.38, p = 0.921) and dominant models (OR = 0.98, 95% CI 0.69-1.40, p = 0.919). Begg's funnel plot and Egger's test have not shown publication bias (p = 0.332). Conclusion: To the best of our knowledge, this is the first meta-analysis that evaluates the relationship between the NPY rs16139 polymorphism and the risk of alcoholism. Our large-scale meta-analysis suggests that NPY rs16139 polymorphism is not associated with alcoholism. However, further studies are needed to increase our understanding of the relationship between NPY variants in alcoholism.

Physical Activity and Nutritional Influence on Immune Function: An Important Strategy to Improve Immunity and Health Status.

Physical activity (PA) and nutrition are the essential components of a healthy lifestyle, as they can influence energy balance, promote functional ability of various systems and improve immunity. Infections and their associated symptoms are the common and frequent challenges to human health that are causing severe economic and social consequences around the world. During aging, human immune system undergoes dramatic aging-related changes/dysfunctions known as immunosenescence. Clinically, immunosenescence refers to the gradual deterioration of immune system that increases exposure to infections, and reduces vaccine efficacy. Such phenomenon is linked to impaired immune responses that lead to dysfunction of multiple organs, while lack of physical activity, progressive loss of muscle mass, and concomitant decline in muscle strength facilitate immunosenescence and inflammation. In the present review, we have discussed the role of nutrition and PA, which can boost the immune system alone and synergistically. Evidence suggests that long-term PA is beneficial in improving immune system and preventing various infections. We have further discussed several nutritional strategies for improving the immune system. Unfortunately, the available evidence shows conflicting results. In terms of interaction with food intake, PA does not tend to increase energy intake during a short time course. However, overcoming nutritional deficiencies appears to be the most practical recommendation. Through the balanced nutritious diet intake one can fulfill the bodily requirement of optimal nutrition that significantly impacts the immune system. Supplementation of a single nutrient as food is generally not advisable. Rather incorporating various fruits and vegetables, whole grains, proteins and probiotics may ensure adequate nutrient intake. Therefore, multi-nutrient supplements may benefit people having deficiency in spite of sufficient diet. Along with PA, supplementation of probiotics, bovine colostrum, plant-derived products and functional foods may provide additional benefits in improving the immune system.

Interleukin-6 gene -174G>C promoter polymorphism reduces the risk of periodontitis in Brazilian populations: A meta-analysis.

INTRODUCTION: Periodontitis is a multifactorial host-mediated oral disease caused by microbes. Previous studies suggested that interleukin-6 (IL-6) gene promoter polymorphism (-174G > C) are associated with the risk of periodontitis, although the results were inconclusive. This study investigated the association between IL-6 -174G > C polymorphism and susceptibility to periodontitis. METHOD: A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and Google Scholar databases to retrieve relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association between 174G > C polymorphism and the risk of periodontitis. Cochrane Q and I2 statistics were used to measure heterogeneity between studies. Publication bias was estimated using Begg's funnel plots and Egger's test. RESULTS: Our results showed significant differences in the allelic (C vs. G: OR = 0.82, CI = 0.65-1.03), recessive (CC vs. GC + GG: OR = 0.69, CI = 0.42-1.13), and dominant (GC + CC vs. GG: OR = 0.85, CI = 0.63-1.13) genetic models of the IL6 -174G > C polymorphism and risk of periodontitis. Further, subgroup analysis showed decreased susceptibility to periodontitis associated with IL6 -174 G > C in a Brazilian population (C vs. G: OR = 0.60, CI = 0.41-0.88; GC + CC vs. GG: OR = 0.57, CI = 0.42-0.78) but not in Asian or Caucasian populations. CONCLUSION: The findings of this study revealed that the IL6 -174 "C" allele is protective against periodontitis in the Brazilian population.

Molecular mechanism, diagnosis, and potential treatment for novel coronavirus (COVID-19): a current literature review and perspective.

Novel coronavirus disease 2019 (COVID-19) is a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. COVID-19 outbreak became evident after the severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus in the twenty-first century as the start of the third deadly coronavirus. Currently, research is at an early stage, and the exact etiological dimensions of COVID-19 are unknown. Several candidate drugs and plasma therapy have been considered and evaluated for the treatment of severe COVID-19 patients. These include clinically available drugs such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir. However, understanding the pathogenic mechanisms of this virus is critical for predicting interaction with humans. Based on recent evidence, we have summarized the current virus biology in terms of the possible understanding of the various pathophysiologies, molecular mechanisms, recent efficient diagnostics, and therapeutic approaches to control the disease. In addition, we briefly reviewed the biochemistry of leading candidates for novel therapies and their current status in clinical trials. As information from COVID-19 is evolving rapidly, this review will help the researcher to consider new insights and potential therapeutic approaches based on up-to-date knowledge. Finally, this review illustrates a list of alternative therapeutic solutions for a viral infection.

Diagnostic and Prognostic Implications of Cardiac Markers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HC) is a malignant primary liver cancer which has poor treatment outcomes in advanced stages, and many of the HC patients present with advanced stages. The incidence of death due to HC increase as a result of ineffective treatments for advanced stage disease. Early diagnosis and management has proven benefits in both survival and quality of life. Currently very few biomarkers are available to provide diagnostic and prognostic benefits in HC patients. The present review elaborates the association of cardiac markers in HC disease. The HC disease pathology includes many cardiovascular events like hypoxia and other parameters discussed in this review which have a role in disease advancement, and also may help as diagnostic and / or prognostic markers. The scientific lacuna in association / role of cardiac markers in HC disease is also stated in this review which may be helpful for future research studies and develop cost effective biomarker for early diagnosis of HC.

Erythrocyte microRNAs: a tiny magic bullet with great potential for sickle cell disease therapy.

Sickle cell disease (SCD) is a severe hereditary blood disorder caused by a mutation of the beta-globin gene, which results in a substantial reduction in life expectancy. Many studies are focused on various novel therapeutic strategies that include re-activation of the γ-globin gene. Among them, expression therapy caused by the fetal hemoglobin (HbF) at a later age is highly successful. The induction of HbF is one of the dominant genetic modulators of the hematological and clinical characteristics of SCD. In fact, HbF compensates for the abnormal beta chain and has an ameliorant effect on clinical complications. Erythropoiesis is a multi-step process that involves the proliferation and differentiation of a small population of hematopoietic stem cells and is affected by several factors, including signaling pathways, transcription factors, and small non-coding RNAs (miRNAs). miRNAs play a regulatory role through complex networks that control several epigenetic mechanisms as well as the post-transcriptional regulation of multiple genes. In this review, we briefly describe the current understanding of interactions between miRNAs, their molecular targets, and their regulatory effects in HbF induction in SCD.

Tumor Necrosis Factor-Alpha Gene Promoter (TNF-α G-308A) Polymorphisms Increase the Risk of Hepatocellular Carcinoma in Asians: A Meta-Analysis.

Hepatocellular carcinoma (HCC) is one of the most common primary hepatic tumors, and it is ranked as the third most common cause of cancer-linked deaths. Although the precise etiology of HCC is unknown, inflammation has been considered the foremost cause of HCC. Previous studies indicated that tumor necrosis factor-alpha (TNF-α) is associated with increased risk of HCC, but the results are conflicting. In the present study, we assessed the correlation between TNF-α G-308A polymorphism as well as HCC risk via a meta-analysis. We searched databases such as PubMed, EMBASE, and Web of Science for articles related to this subject. To evaluate the correlation between TNF-α G-308A polymorphism and HCC, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Between-study heterogeneity was assessed using Cochrane Q test and I2 statistics. To assess the robustness of data, sensitivity analysis, publication bias, and subgroup analysis were conducted. Approximately 30 articles with 4,753 cases of HCC and 6,667 controls were included for the meta-analysis. Overall, the TNF-α G-308A polymorphism notably correlated with increased risk of HCC in the dominant model (OR = 1.41, 95% CI: 1.02-1.94, P = 0.036). Furthermore, a subgroup investigation showed significant correlation between TNF-α G-308A polymorphisms and HCC risk only in Asian populations (dominant model OR = 1.55, 95% CI: 1.05-2.23, P = 0.025). Studies in ethnic groups showed significant heterogeneity (I2 > 50%). Funnel plot and Eggers p values did not reveal publication bias. The present meta-analysis suggested that TNF-α G-308A polymorphisms are correlated with an elevated risk of HCC in Asian populations.

Dynamic Propagation and Impact of Pandemic Influenza A (2009 H1N1) in Children: A Detailed Review.

Influenza is a highly contagious respiratory infection caused by the circulating Swine flu virus. According to the World Health Organization (WHO), the unique blending strain of influenza A H1N1 2009 (Swine Flu) is a pandemic affecting several geographical regions, including India. Previous literature indicates that children are "drivers" of influenza pandemics. At present, satisfactory data were not available to accurately estimate the role of children in the spread of influenza (in particular 2009 pandemic influenza). However, the role of children in the spread of pandemics influenza is unclear. Several studies in children have indicated that the immunization program decreased the occurrence of influenza, emphasizing the significance of communities impacted by global immunization programs. This article provides a brief overview on how children are a key contributor to pandemic Influenza A (2009 H1N1) and we would like to draw your attention to the need for a new vaccine for children to improve disease prevention and a positive impact on the community.

Current updates on the European and WHO registered clinical trials of coronavirus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) is a major public health concern currently. To date, there are no approved antiviral drugs or vaccines against this transmissible disease. This report sheds light on available information for a better understanding of clinical trials and pharmacotherapy related to COVID-19. MEDLINE, PubMed, EMBASE, Scopus databases, Web of Science, WHO, and EU clinical trial sites were used to perform comparative analysis. Information was collected on the use of therapeutic agents for human therapy in patients with COVID-19 up to May 2020. We have extracted data from 60 clinical trials. Amongst these trials, 34 were from the European Union database of clinical trials and 26 from the National Institute of Health. The data selection procedure includes active, completed, and recruitment in progress status. Most of the clinical trials are ongoing and hence, there is a lack of precise results for the treatment.There is a lack of high-quality clinical evidence. The protocol to be developed requires large randomized clinical trials with a combination of available drugs and prospective therapies. We propose the usage of a large number of cases and different statistical analyses to conduct systematic clinical trials. This could provide comprehensive information about the clinical trial and potential therapeutic progress.