Chemotherapy's effects on autophagy in the treatment of Hodgkin's lymphoma: a scoping review.

BACKGROUND: Classical Hodgkin Lymphomas (HL) are a unique malignant growth with an excellent initial prognosis. However, 10-30% of patients will still relapse after remission. One primary cellular function that has been the focus of tumor progression is autophagy. This process can preserve cellular homeostasis under stressful conditions. Several studies have shown that autophagy may play a role in developing HL. Therefore, this review aimed to explore chemotherapy's effect on autophagy in HL, and the effects of autophagy on HL. METHODS: A scoping review in line with the published PRISMA extension for scoping reviews (PRISMA-ScR) was conducted. A literature search was conducted on the MEDLINE database and the Cochrane Central Register of Controlled Trials (CENTRAL). All results were retrieved and screened, and the resulting articles were synthesized narratively. RESULTS: The results showed that some cancer chemotherapy also induces autophagic flux. Although the data on HL is limited, since the mechanisms of action of these drugs are similar, we can infer a similar relationship. However, this increased autophagy activity may reflect a mechanism for increasing tumor growth or a cellular compensation to inhibit its growth. Although evidence supports both views, we argued that autophagy allowed cancer cells to resist cell death, mainly due to DNA damage caused by cytotoxic drugs. CONCLUSION: Autophagy reflects the cell's adaptation to survive and explains why chemotherapy generally induces autophagy functions. However, further research on autophagy inhibition is needed as it presents a viable treatment strategy, especially against drug-resistant populations that may arise from HL chemotherapy regimens.

The heterogeneity of breast cancer metastasis: a bioinformatics analysis utilizing single-cell RNA sequencing data.

PURPOSE: Breast cancer is a common malignancy in women, and its metastasis is a leading cause of cancer-related deaths. Single-cell RNA sequencing (scRNA-seq) can distinguish the molecular characteristics of metastasis and identify predictor genes for patient prognosis. This article explores gene expression in primary breast cancer tumor tissue against metastatic cells in the lymph node and liver using scRNA-seq. METHODS: Breast cancer scRNA-seq data from the Gene Expression Omnibus were used. The data were processed using R and the Seurat package. The cells were clustered and identified using Metascape. InferCNV is used to analyze the variation in copy number. Differential expression analysis was conducted for the cancer cells using Seurat and was enriched using Metascape. RESULTS: We identified 18 distinct cell clusters, 6 of which were epithelial. CNV analysis identified significant alterations with duplication of chromosomes 1, 8, and 19. Differential gene analysis resulted in 17 upregulated and 171 downregulated genes for the primary tumor in the primary tumor vs. liver metastasis comparison and 43 upregulated and 4 downregulated genes in the primary tumor in the primary tumor vs lymph node metastasis comparison. Several enriched terms include Ribosome biogenesis, NTP synthesis, Epithelial dedifferentiation, Autophagy, and genes associated with epithelial-to-mesenchymal transitions. CONCLUSION: No single gene or pathway can clearly explain the mechanisms behind tumor metastasis. Several mechanisms contribute to lymph node and liver metastasis, such as the loss of differentiation, epithelial-to-mesenchymal transition, and autophagy. These findings necessitate further study of metastatic tissue for effective drug development.

Physiological Roles of Hippo Signaling Pathway and Autophagy in Dementia.

BACKGROUND: Dementia is a neurocognitive disorder associated with the aging brain and mainly affects the hippocampus and cerebral cortex. The Hippo signaling pathway and autophagy proteins have been found to be perturbed in the brain affected by dementia processes. OBJECTIVE: This systematic review aims to elaborate on the involvement of the Hippo signaling pathway and autophagy in modulating the progression and severity of dementia in aging. METHODS: Searches were conducted on MEDLINE, Google Scholar, Scopus, and Web of Science databases. RESULTS: The Hippo signaling pathway is dependent upon the transcriptional co-activator YAP/TAZ, which forms complexes with TEAD in the nucleus in order to maintain cell homeostasis. When the expression YAP/TAZ is reduced, transcriptional repression-induced atypical cell death, ballooning cell death, and necrosis will consequently occur in the neurons. Moreover, the autophagic proteins, such as LC3, ATG proteins, and Beclin, are reduced, resulting in the disruption of autophagosome formation and accumulation and the spread of misfolded proteins in the brain suffering from dementia. CONCLUSION: The impairment of the Hippo signaling pathway and autophagy in the dementia process in aging should be considered since it might predict the severity, treatment, and prevention of dementia.

Impact of COVID-19 pandemic on medical students: a scoping review protocol.

INTRODUCTION: The COVID-19 pandemic has spread globally and has been reported in every known country. The effects can be felt in universities and schools, shifting their learning to online platforms. However, medical schools bear the burden of protecting students and ensuring the continuation of the education process. The rapid transition to online learning, coupled with the lack of preparation from the educational system, leads to stresses that affect students' academic performance, mental health and social life. Nevertheless, no review tried to synthesise the complete picture of the pandemic's effects. Therefore, this scoping review aims to identify and explore the available literature on the effects or impacts of the pandemic on medical students without limiting it to specific dimensions. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and the Joanna Briggs Institute manual for evidence synthesis. We examine articles reporting data from any country. However, only articles written in English will be included. For studies to be included, they must report any form of impact on medical students, qualitatively or quantitatively. Furthermore, the impact must occur within the context of the COVID-19 pandemic. Searches will be done on Medline, EMBASE, ERIC, the Cochrane Library, CINAHL and PsycInfo. After data extraction, we will narratively synthesise the data and explore the types of impacts COVID-19 has on medical students. ETHICS AND DISSEMINATION: No formal ethical approval is required. The scoping review will be published in peer-reviewed journals and as conference presentations and summaries, wherever appropriate.

Potential Role of Exercise in Regulating YAP and TAZ During Cardiomyocytes Aging.

Adaptation of cardiac muscle to regular exercise results in morphological and structural changes known as physiological cardiac hypertrophy, to which the Hippo signaling pathway might have contributed. Two major terminal effectors in the Hippo signaling pathway are Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ). The latest studies have reported the role of YAP and TAZ in different life stages, such as in fetal, neonatal, and adult hearts. Their regulation might involve several mechanisms and effectors. One of the possible coregulators is exercise. Exercise plays a role in cardiomyocyte hypertrophic changes during different stages of life, including in aged hearts. YAP/TAZ signaling pathway has a role in physiological cardiac hypertrophy induced by exercise and is associated with cardiac remodelling. Thus, it can be believed that exercise has roles in activating the signaling pathway of YAP and TAZ in aged cardiomyocytes. However, the studies regarding the roles of YAP and TAZ during cardiomyocyte aging are limited. The primary purpose of this review is to explore the response of cardiovascular aging to exercise via signaling pathway of YAP and TAZ.

Elaborating the Physiological Role of YAP as a Glucose Metabolism Regulator:A Systematic Review.

Yes-associated protein (YAP) is one of the Hippo pathway's two effectors, a pathway associated with organ size control. Research on YAP has focused on its oncogenic potential. However, in cancer cells, aside from inducing growth, YAP was also found to regulate glucose metabolism. The present review explores YAP's control of glucose metabolism and whether these findings are translatable to physiological conditions. According to current literature, YAP induces the transcriptional activity of most genes associated with glucose metabolism from enzymes to transport proteins. In glycolysis and gluconeogenesis, YAP upregulates all enzymes except for enolase and pyruvate kinase. Multiple research has also shown YAP's ability to regulate the expression of glucose transporter of the GLUT family. Additionally, glucose concentration, hypoxia, and hormones such as insulin and glucagon regulate YAP activity and depend on YAP to exert their biological activity. YAP is thus a central regulator of glucose metabolism, controlling both enzymes and proteins involved in glucose transport. YAP is also situated strategically in several pathways controlling glucose and was found to mediate their effects. If these results were consistent in physiological conditions and across glucose-associated metabolic disturbances, then YAP may become a prospective therapeutic target.

Hippo pathway effectors YAP and TAZ and their association with skeletal muscle ageing.

Skeletal muscle atrophy commonly occurs during ageing, thus pathways that regulate muscle mass may represent a potential therapeutic avenue for interventions. In this review, we explored the Hippo signalling pathway which plays an essential role in human oncogenesis and the pathway's influence on myogenesis and satellite cell functions, on supporting cells such as fibroblasts, and autophagy. YAP/TAZ was found to regulate both myoblast proliferation and differentiation, albeit with unique roles. Additionally, YAP/TAZ has different functions depending on the expressing cell type, making simple inference of their effects difficult. Studies in cancers have shown that the Hippo pathway influenced the autophagy pathway, although with mixed results. Most of the present researches on YAP/TAZ are focused on its oncogenicity and further studies are needed to translate these findings to physiological ageing. Taken together, the modulation of YAP/TAZ or the Hippo pathway in general may offer potential new strategies for the prevention or treatment of ageing.

Meralgia paresthetica: finding an effective cure.

Meralgia Paresthetica (MP) is one of the most common mononeuropathies of the lower limb. MP usually resolves on its own, even without treatment. However, many physicians are not aware of this diagnosis and may confuse patients with another nerve disease such as radiculopathies. Although no motor symptoms are associated with this condition, the sensory dysfunctions are potentially debilitating to patients. The variable course of the lateral femoral cutaneous nerve also complicates treatments. Thus, the author recommends the use of ultrasonography to help locate the nerve. Many treatments for MP are available, but they are supported only by moderate to low-quality evidence. Treatments range from conservative to interventions using nerve blocks and surgery. Without a clear superiority of any treatment, the author concludes that treatment should be done in a stepwise fashion, from the noninvasive to the more invasive treatment if symptoms persist.