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OBJECTIVES: To determine the dysregulated signaling pathways of head and neck squamous cell carcinoma associated with circulating tumor cells (CTCs) via single-cell molecular characterization. INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) has a significant global burden and is a disease with poor survival. Despite trials exploring new treatment modalities to improve disease control rates, the 5 year survival rate remains low at only 60%. Most cancer malignancies are reported to progress to a fatal phase due to the metastatic activity derived from treatment-resistant cancer cells, regarded as one of the most significant obstacles to develope effective cancer treatment options. However, the molecular profiles of cancer cells have not been thoroughly studied. METHODS: Here, we examined in-situ HNSCC tumors and pairwisely followed up with the downstream circulating tumor cells (CTCs)-based on the surrogate biomarkers to detect metastasis that is established in other cancers - not yet being fully adopted in HNSCC treatment algorithms. RESULTS: Specifically, we revealed metastatic HNSCC patients have complex CTCs that could be defined through gene expression and mutational gene profiling derived from completed single-cell RNASeq (scRNASeq) that served to confirm molecular pathways inherent in these CTCs. To enhance the reliability of our findings, we cross-validated those molecular profiles with results from previously published studies. CONCLUSION: Thus, we identified 5 dysregulated signaling pathways in CTCs to derive HNSCC biomarker panels for screening HNSCC in situ tumors.

Objective: This study aimed to find global mechanisms related to carnosine synthesis in slow-growing Korat chickens (KRC) using a proteomic approach. Methods: M. pectoralis major samples were collected from 10-week-old female KRC including low-carnosine (LC, 2,756.6±82.88 μg/g; n = 5) and high-carnosine (HC, 4,212.5 ±82.88 μg/g; n = 5). Results: We identified 152 common proteins, and 8 of these proteins showed differential expression between the LC and HC groups (p<0.05). Heat shock 70 kDa protein 8, Heat shock 70 kDa protein 2, protein disulfide isomerase family A, member 6, and endoplasmic reticulum resident protein 29 were significantly involved in protein processing in the endoplasmic reticulum pathway (false discovery rate<0.05), suggesting that the pathway is related to differential carnosine concentration in the M. pectoralis major of KRC. A high concentration of carnosine in the meat is mainly involved in low abundances of Titin isoform Ch12 and Connectin and high abundances of M-protein to maintain homeostasis during muscle contraction. These consequences improve meat characteristics, which were confirmed by the principal component analysis. Conclusion: Carnosine synthesis may occur when muscle cells need to recover homeostasis after being interfered with carnosine synthesis precursors, leading to improved muscle function. To the best of our knowledge, this is the first study to describe in detail the global molecular mechanisms in divergent carnosine contents in meat based on the proteomic approach. [ABSTRACT FROM AUTHOR]

Owing to the recent emergence of COVID-19, there is a lack of published research and clinical recommendations for posttraumatic stress disorder (PTSD) risk factors in patients who contracted or received treatment for the virus. This research aims to identify potential molecular targets to inform therapeutic strategies for this patient population. RNA sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and PTSD (from the National Center for Biotechnology Information [NCBI]) were processed using the GREIN database. Protein-protein interaction (PPI) networks, pathway enrichment analyses, miRNA interactions, gene regulatory network (GRN) studies, and identification of linked drugs, chemicals, and diseases were conducted using STRING, DAVID, Enrichr, Metascape, ShinyGO, and NetworkAnalyst v3.0. Our analysis identified 15 potentially unique hub proteins within significantly enriched pathways, including PSMB9, MX1, HLA-DOB, HLA-DRA, IFIT3, OASL, RSAD2, and so on, filtered from a pool of 201 common differentially expressed genes (DEGs). Gene ontology (GO) terms and metabolic pathway analyses revealed the significance of the extracellular region, extracellular space, extracellular exosome, adaptive immune system, and interleukin (IL)-18 signaling pathways. In addition, we discovered several miRNAs (hsa-mir-124-3p, hsa-mir-146a-5p, hsa-mir-148b-3p, and hsa-mir-21-3p), transcription factors (TF) (WRNIP1, FOXC1, GATA2, CREB1, and RELA), a potentially repurposable drug carfilzomib and chemicals (tetrachlorodibenzodioxin, estradiol, arsenic trioxide, and valproic acid) that could regulate the expression levels of hub proteins at both the transcription and posttranscription stages. Our investigations have identified several potential therapeutic targets that elucidate the probability that victims of COVID-19 experience PTSD. However, they require further exploration through clinical and pharmacological studies to explain their efficacy in preventing PTSD in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Levodopa is the most widely used medication for the symptomatic treatment of Parkinson’s disease and, despite being an “old” drug, is still considered the gold standard for offering symptomatic relief. The pharmacokinetic and pharmacodynamics of levodopa have been studied extensively. Our review explores the molecular mechanisms that affect the absorption of this drug, focusing on the large intra- and interindividual variability of absorption that is commonly encountered in daily clinical practice, and on the interaction with other medications. In addition, we will explore the clinical implications of levodopa absorption variability and address current and future strategies for researchers and clinicians. [ABSTRACT FROM AUTHOR]

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants. [ABSTRACT FROM AUTHOR]

Objective This study aimed to find global mechanisms related to carnosine synthesis in slow-growing Korat chickens (KRC) using a proteomic approach. Methods M. pectoralis major samples were collected from 10-week-old female KRC including low-carnosine (LC, 2,756.6±82.88 μg/g; n = 5) and high-carnosine (HC, 4,212.5 ±82.88 μg/g; n = 5). Results We identified 152 common proteins, and 8 of these proteins showed differential expression between the LC and HC groups (p

Cardiotoxicity is a serious challenge cancer patients face today. Various factors are involved in cardiotoxicity. Circular RNAs (circRNAs) are one of the effective factors in the occurrence and prevention of cardiotoxicity. circRNAs can lead to increased proliferation, apoptosis, and regeneration of cardiomyocytes by regulating the molecular pathways, as well as increasing or decreasing gene expression; some circRNAs have a dual role in cardiomyocyte regeneration or death. Identifying each of the pathways related to these processes can be effective on managing patients and preventing cardiotoxicity. In this study, an overview of the molecular pathways involved in cardiotoxicity by circRNAs and their effects on the downstream factors have been discussed. [ABSTRACT FROM AUTHOR]

Abstract GNAO1 encodes G protein subunit alpha O1 (Gαo). Pathogenic variations in GNAO1 cause developmental delay, intractable seizures, and progressive involuntary movements from early infancy. Because the functional role of GNAO1 in the developing brain remains unclear, therapeutic strategies are still unestablished for patients presenting with GNAO1-associated encephalopathy. We herein report that siRNA-mediated depletion of Gnao1 perturbs the expression of transcripts associated with Rho GTPase signaling in Neuro2a cells. Consistently, siRNA treatment hampered neurite outgrowth and extension. Growth cone formation was markedly disrupted in monolayer neurons differentiated from iPSCs from a patient with a pathogenic variant of Gαo (p.G203R). This variant disabled neuro-spherical assembly, acquisition of the organized structure, and polarized signals of phospho-MLC2 in cortical organoids from the patient’s iPSCs. We confirmed that the Rho kinase inhibitor Y27632 restored these morphological phenotypes. Thus, Gαo determines the self-organizing process of the developing brain by regulating the Rho-associated pathway. These data suggest that Rho GTPase pathway might be an alternative target of therapy for patients with GNAO1-associated encephalopathy.

GNAO1 encodes G protein subunit alpha O1 (Gαo). Pathogenic variations in GNAO1 cause developmental delay, intractable seizures, and progressive involuntary movements from early infancy. Because the functional role of GNAO1 in the developing brain remains unclear, therapeutic strategies are still unestablished for patients presenting with GNAO1-associated encephalopathy. We herein report that siRNA-mediated depletion of Gnao1 perturbs the expression of transcripts associated with Rho GTPase signaling in Neuro2a cells. Consistently, siRNA treatment hampered neurite outgrowth and extension. Growth cone formation was markedly disrupted in monolayer neurons differentiated from iPSCs from a patient with a pathogenic variant of Gαo (p.G203R). This variant disabled neuro-spherical assembly, acquisition of the organized structure, and polarized signals of phospho-MLC2 in cortical organoids from the patient’s iPSCs. We confirmed that the Rho kinase inhibitor Y27632 restored these morphological phenotypes. Thus, Gαo determines the self-organizing process of the developing brain by regulating the Rho-associated pathway. These data suggest that Rho GTPase pathway might be an alternative target of therapy for patients with GNAO1-associated encephalopathy. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading cause of disability worldwide, with an estimated annual incidence of 27–69 million. TBI is a severe condition that can lead to high mortality rates and long-term cognitive, behavioral, and physical impairments in young adults. It is a significant public health concern due to the lack of effective treatments available. Quercetin, a natural flavonoid found in various fruits and vegetables, has demonstrated therapeutic potential with anti-inflammatory, antioxidant, and neuroprotective properties. Recently, some evidence has accentuated the ameliorating effects of quercetin on TBI. This review discusses quercetin's ability to reduce TBI-related damage by regulating many cellular and molecular pathways. Quercetin in vitro and in vivo studies exhibit promise in reducing inflammation, oxidative stress, apoptosis, and enhancing cognitive function post-TBI. Further clinical investigation into quercetin's therapeutic potential as a readily available adjuvant in the treatment of TBI is warranted in light of these findings. This review adds to our knowledge of quercetin's potential in treating TBI by clarifying its mechanisms of action. [ABSTRACT FROM AUTHOR]

Elevated plasma fibrinogen (Fg) levels consistently correlate with an unfavorable prognosis in various tumor patient cohorts. Within the tumor microenvironment, aberrant deposition and expression of Fg have been consistently observed, interacting with multiple cellular receptors and thereby accentuating its role as a regulator of inflammatory processes. Specifically, Fg serves to stimulate and recruit immune cells and pro-inflammatory cytokines, thereby contributing to the promotion of tumor progression. Additionally, Fg and its fragments exhibit dichotomous effects on tumor angiogenesis. Notably, Fg also facilitates tumor migration through both platelet-dependent and platelet-independent mechanisms. Recent studies have illuminated several tumor-related signaling pathways influenced by Fg. This review provides a comprehensive summary of the intricate involvement of Fg in tumor biology, elucidating its multifaceted role and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25–30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively. [ABSTRACT FROM AUTHOR]

Platelets are one of the coagulation cells. When platelet activation occurs, many mediators are released and affect endothelial cells (ECs) and lead to endothelial dysfunction (ED). ED plays an important role in the pathogenesis of many diseases, including cardiovascular disease (CVD). Platelet are of important factors in ED. The release of mediators by platelets causes the stimulation of inflammatory pathways, oxidative stress, and apoptosis, which ultimately result in ED. On the other hand, platelet activation in CVD patients can be associated with a bad prognosis. Platelet activation can increase the level of markers such as p-selectin in the serum. Also, in this study, we have discussed the role of platelet as a diagnostic factor, as well as its use as a treatment option. In addition, we discussed some of the molecular pathways that are used to target platelet activation. [ABSTRACT FROM AUTHOR]

Minocycline is an FDA-approved secondary-generation tetracycline antibiotic. It is a synthetic antibiotic having many biological effects, such as antioxidant, anti-inflammatory, anti-cancer, and neuroprotective functions. This study discusses the pharmacological mechanisms of preventive and therapeutic effects of minocycline. Specifically, it provides a comprehensive overview of the molecular pathways by which minocycline acts on the different cancers, including ovarian, breast, glioma, colorectal, liver, pancreatic, lung, prostate, melanoma, head and neck, leukemia, and non-cancer diseases such as Alzheimer's disease, Parkinson, schizophrenia, multiple sclerosis, Huntington, polycystic ovary syndrome, and coronavirus disease 19. Minocycline may be a potential medication for these disorders due to its strong blood–brain barrier penetrance. It is also widely accepted as a specific medication, has a well-known side-effect characteristic, is reasonably priced, making it appropriate for continuous use in managing diseases, and has been demonstrated as an oral approach because it is effectively absorbed and accomplished almost all of the body's parts. [ABSTRACT FROM AUTHOR]

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

Introduction: Over the past decades, immune dysregulation has been consistently demonstrated being common charactoristics of endometriosis (EM) and Inflammatory Bowel Disease (IBD) in numerous studies. However, the underlying pathological mechanisms remain unknown. In this study, bioinformatics techniques were used to screen large-scale gene expression data for plausible correlations at the molecular level in order to identify common pathogenic pathways between EM and IBD. Methods: Based on the EM transcriptomic datasets GSE7305 and GSE23339, as well as the IBD transcriptomic datasets GSE87466 and GSE126124, differential gene analysis was performed using the limma package in the R environment. Coexpressed differentially expressed genes were identified, and a protein-protein interaction (PPI) network for the differentially expressed genes was constructed using the 11.5 version of the STRING database. The MCODE tool in Cytoscape facilitated filtering out protein interaction subnetworks. Key genes in the PPI network were identified through two topological analysis algorithms (MCC and Degree) from the CytoHubba plugin. Upset was used for visualization of these key genes. The diagnostic value of gene expression levels for these key genes was assessed using the Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) The CIBERSORT algorithm determined the infiltration status of 22 immune cell subtypes, exploring differences between EM and IBD patients in both control and disease groups. Finally, different gene expression trends shared by EM and IBD were input into CMap to identify small molecule compounds with potential therapeutic effects. Results: 113 differentially expressed genes (DEGs) that were co-expressed in EM and IBD have been identified, comprising 28 down-regulated genes and 86 upregulated genes. The co-expression differential gene of EM and IBD in the functional enrichment analyses focused on immune response activation, circulating immunoglobulin-mediated humoral immune response and humoral immune response. Five hub genes (SERPING1,VCAM1,CLU,C3,CD55) were identified through the Protein-protein Interaction network and MCODE.High Area Under the Curve (AUC) values of Receiver Operating Characteristic (ROC) curves for 5hub genes indicate the predictive ability for disease occurrence. These hub genes could be used as potential biomarkers for the development of EM and IBD. Furthermore, the CMap database identified a total of 9 small molecule compounds (TTNPB,CAY-10577,PD-0325901 etc.) targeting therapeutic genes for EM and IBD. Discussion: Our research revealed common pathogenic mechanisms between EM and IBD, particularly emphasizing immune regulation and cell signalling, indicating the significance of immune factors in the occurence and progression of both diseases. By elucidating shared mechanisms, our study provides novel avenues for the prevention and treatment of EM and IBD. [ABSTRACT FROM AUTHOR]

Dopamine is a hormone that is released by the adrenal gland and influences motor control and motivation. Dopamine is known to have 5 receptors which are D1, D2, D3, D4 and D5, which are further categorized into 2 families: D1 family and D2 family. The D1 family is known to play a role in motivation and motor control whereas the D2 family is known to affect attention and sleep. THC, a type of cannabinoid, can lead to feelings of euphoria, anxiety, fear, distrust, or panic. THC is known to affect dopamine in regions such as the anterior cingulate cortex (ACC), and plays a role in fundamental cognitive processes. Although there is a vast amount of research between the relationship of THC on dopamine, there continues to be limited research in relation to THC on dopamine receptors. The D1 receptor plays a role in several essential functions, such as memory, attention, impulse control, regulation of renal function, and locomotion. Accordingly, this review is intended to summarize the relationship between THC and D1 receptors, highlighting key gaps in the literature and avenues for future research. [ABSTRACT FROM AUTHOR]

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a distinct subtype of T-cell non-Hodgkin lymphoma that arises in the context of prolonged exposure to textured breast implants. The intent of this manuscript is to explore whether the bacterial presence in biofilms on these implants is a mere incidental finding or plays a pivotal role in the pathogenesis of BIA-ALCL. Our goal is to delineate the extent of bacterial involvement, offering insights into potential underlying mechanisms, and establishing future research priorities aimed at resolving the remaining uncertainties surrounding this complex association. A comprehensive systematic review of several databases was performed. The search strategy was designed and conducted by an experienced librarian using controlled vocabulary with keywords. The electronic search identified 442 publications. After evaluation, six studies from 2015 to 2021 were included, encompassing 201 female patients aged 23 to 75. The diagnosis span post-implantation ranged from 53 to 135.6 months. Studies consistently found bacteria near breast implants in both BIA-ALCL cases and controls, with varied microbial findings. Both BIA-ALCL cases and controls exhibited the presence of specific bacteria, including Pseudomonas aeruginosa, Klebsiella oxytoca, Staphylococcus aureus, and Ralstonia spp., without any statistically significant differences between groups. The use of antiseptic and antimicrobial agents during implant insertion did not demonstrate any impact on reducing or altering the risk of developing BIA-ALCL. Our systematic review reveals that the current evidence is inadequate to link bacterial etiology as a central factor in the development of BIA-ALCL. The limitations in the existing data prevent a complete dismissal of the role of biofilms in its pathogenesis. The observed gap in knowledge underscores the need for more focused and comprehensive research, which should be structured in a multi-faceted approach. Initially, this involves the utilization of sophisticated genomic and proteomic methods. Following this, it is crucial to delve into the study of immunological reactions specifically induced by biofilms. Finally, this research should incorporate extended observational studies, meticulously tracking the evolution of biofilm development and its correlation with the emergence of BIA-ALCL. In light of the inconclusive nature of current findings, further investigation is not only justified but urgently needed to clarify these unresolved issues. [ABSTRACT FROM AUTHOR]

HELLP syndrome is a disorder during pregnancy which is defined by elevation of liver enzymes, haemolysis, and low platelet count. This syndrome is a multifactorial one and both genetic and environmental components can have a crucial role in this syndrome's pathogenesis. Long noncoding RNAs (lncRNAs), are defined as long non-protein coding molecules (more than 200 nucleotides), which are functional units in most cellular processes such as cell cycle, differentiation, metabolism and some diseases progression. As these markers discovered, there has been some evidence that they have an important role in the function of some organs, such as placenta; therefore, alteration and dysregulation of these RNAs can develop or alleviate HELLP disorder. Although the role of lncRNAs has been shown in HELLP syndrome, the process is still unclear. In this review, our purpose is to evaluate the association between molecular mechanisms of lncRNAs and HELLP syndrome pathogenicity to elicit some novel approaches for HELLP diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Depending on extent and depth, burn injuries and resulting scars may be challenging and expensive to treat and above all heavily impact the patients' lives. This systematic review represents the current state of knowledge on molecular pathways activated during burn wound healing. All currently known molecular information about gene expression and molecular interactions in mammals has been summarized. An ample interaction of regenerative cytokines, growth factors, ECM-regenerative molecules and proinflammatory immune response became apparent. We identified three molecules to be most often involved in the pathways: TGFB1, ACTA1 and COL1A1. Yet, other factors including FLII, AKT1 and miR-145 were shown to play pivotal roles in burn wound healing as well. This systematic review helps to explain the fundamental molecular proceedings participating in burn wound healing. A number of new molecular interactions and functional connections were identified yielding intriguing new research targets. An interactive version of the first network about molecular pathways and interactions during burn wound healing is provided in the online edition and on WikiPathways. • Our systematic review gives a comprehensive overview of known molecular interactions during burn wound healing. • Species-specific pathways are independently published as open-access on WikiPathways in a standardized manner. • Novel OMICs and bioinformatic analysis can benefit from our summary. [ABSTRACT FROM AUTHOR]

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs. [ABSTRACT FROM AUTHOR]

Cancer is one of the deadliest and most heterogeneous diseases. Cancers often develop drug resistance, which can lead to treatment failure or recurrence. Accordingly, anticancer compounds are essential for chemotherapy-resistant cancer cells. Phenolic compounds are of interest in the development of cancer drugs due to their medicinal properties and ability to target different molecular pathways. Gallic acid (GA), as one of the main components of phenol, which is abundantly present in plant compounds such as walnut, sumac, grapes, tea leaves, oak bark, and other plant compounds, has antitumor properties. GA can prevent cancer progression, cell invasion, and metastasis by targeting molecular pathways and is an effective complement to chemotherapy drugs and combating multidrug resistance (MDR). In this review, we discuss various mechanisms related to cancer, the therapeutic potential of GA, the antitumor properties of GA in various cancers, and the targeted delivery of GA with nanocarriers. [ABSTRACT FROM AUTHOR]

The prawn Macrobrachium tenellum shows aquaculture potential due to its well-defined reproductive cycle linked to female nutritional requirements. Significant changes occur in egg composition during the 16 to 17-day embryo development. Understanding the ontogenic proteins is crucial for developmental insights and controlled reproduction. We employed free-label quantitative proteomics to analyze egg peptides at the initial and final stages of wild females. Using the emPAI protocol and Proteome Discoverer 2.0, we identified 89 differentially expressed proteins in M. tenellum eggs. Of these, 27 were exclusive to early-stage development and three to late-stage. Abundant proteins included Vitellogenin, glyceraldehyde-3-phosphate dehydrogenase, histone 4, beta-actin, and hemocyanin. Gene Ontology analysis revealed 518 terms across molecular functions, biological processes, and cellular components using the GoRetriever tool of AgBase and the CateGOrizer tool of the Animal Genome Research Program. Carbohydrate metabolism was significant in early-stage development, with glyceraldehyde-3-phosphate dehydrogenase being the second most abundant protein. Proteins involved in ATP synthesis and cytoplasmic proteins associated with catalytic and binding activities related to primary metabolism were also detected. Our study elucidates the role of Vitellogenin in lipid transport activity and its potential involvement in the juvenile hormone feedback pathway. This pathway includes farnesoic acid O-methyltransferase and juvenile hormone epoxide oxidase, regulating protein biosynthesis, molt cycles (including chitinase activity), and potentially influencing controlled reproduction. Our proteomic analysis provides insights into the molecular mechanisms driving Ontogenic development in Macrobrachium tenellum, with implications for controlled reproduction strategies and advancements in aquaculture practices. [ABSTRACT FROM AUTHOR]

Dopamine is a hormone that is released by the adrenal gland and influences motor control and motivation. Dopamine is known to have 5 receptors which are D1, D2, D3, D4 and D5, which are further categorized into 2 families: D1 family and D2 family. The D1 family is known to play a role in motivation and motor control whereas the D2 family is known to affect attention and sleep. THC, a type of cannabinoid, can lead to feelings of euphoria, anxiety, fear, distrust, or panic. THC is known to affect dopamine in regions such as the anterior cingulate cortex (ACC), and plays a role in fundamental cognitive processes. Although there is a vast amount of research between the relationship of THC on dopamine, there continues to be limited research in relation to THC on dopamine receptors. The D1 receptor plays a role in several essential functions, such as memory, attention, impulse control, regulation of renal function, and locomotion. Accordingly, this review is intended to summarize the relationship between THC and D1 receptors, highlighting key gaps in the literature and avenues for future research.

ABSTRACTBerberine is a metabolite of many medicinal plants. Chemically, berberine belongs to the isoquinoline alkaloids family. The roots of plants grown at lower elevations have a higher concentration of berberine as compared to plants grown at higher elevations. Berberine is a natural substance, which is now among the patent pharmaceuticals for reducing chronic disorders and malignancies. Berberine is also classified as a nutraceutical. Nutraceuticals have been associated with various health benefits via modifying microRNA (miR) expression systems, apoptosis, gene activity, chemical signals/pathways and activation of transcription factors thus aiding in the prevention from various ailments. The pharmacokinetic studies revealed that berberine is poorly absorbed via intestinal walls therefore, its concentration level is extremely low in body fluid. However, the quantity of berberine and its active derivatives in organs is higher as compared to blood as it stably present in tissues. Berberine has an effective role in the body as an anticancer, antidiabetic, antiobesity, antioxidant, antiinflammatory, neuroprotective, hepatoprotective, antiaging and cardioprotective agent. In this review, the therapeutic potentials of berberine are discussed to understand its nutraceutical importance.

HELLP syndrome is a disorder during pregnancy which is defined by elevation of liver enzymes, haemolysis, and low platelet count. This syndrome is a multifactorial one and both genetic and environmental components can have a crucial role in this syndrome’s pathogenesis. Long noncoding RNAs (lncRNAs), are defined as long non-protein coding molecules (more than 200 nucleotides), which are functional units in most cellular processes such as cell cycle, differentiation, metabolism and some diseases progression. As these markers discovered, there has been some evidence that they have an important role in the function of some organs, such as placenta; therefore, alteration and dysregulation of these RNAs can develop or alleviate HELLP disorder. Although the role of lncRNAs has been shown in HELLP syndrome, the process is still unclear. In this review, our purpose is to evaluate the association between molecular mechanisms of lncRNAs and HELLP syndrome pathogenicity to elicit some novel approaches for HELLP diagnosis and treatment.

The prawn Macrobrachium tenellum shows aquaculture potential due to its well-defined reproductive cycle linked to female nutritional requirements. Significant changes occur in egg composition during the 16 to 17-day embryo development. Understanding the ontogenic proteins is crucial for developmental insights and controlled reproduction. We employed free-label quantitative proteomics to analyze egg peptides at the initial and final stages of wild females. Using the emPAI protocol and Proteome Discoverer 2.0, we identified 89 differentially expressed proteins in M. tenellum eggs. Of these, 27 were exclusive to early-stage development and three to late-stage. Abundant proteins included Vitellogenin, glyceraldehyde-3-phosphate dehydrogenase, histone 4, beta-actin, and hemocyanin. Gene Ontology analysis revealed 518 terms across molecular functions, biological processes, and cellular components using the GoRetriever tool of AgBase and the CateGOrizer tool of the Animal Genome Research Program. Carbohydrate metabolism was significant in early-stage development, with glyceraldehyde-3-phosphate dehydrogenase being the second most abundant protein. Proteins involved in ATP synthesis and cytoplasmic proteins associated with catalytic and binding activities related to primary metabolism were also detected. Our study elucidates the role of Vitellogenin in lipid transport activity and its potential involvement in the juvenile hormone feedback pathway. This pathway includes farnesoic acid O-methyltransferase and juvenile hormone epoxide oxidase, regulating protein biosynthesis, molt cycles (including chitinase activity), and potentially influencing controlled reproduction. Our proteomic analysis provides insights into the molecular mechanisms driving Ontogenic development in Macrobrachium tenellum, with implications for controlled reproduction strategies and advancements in aquaculture practices.

Abstract Numerous studies have underscored the essential role of sunlight in vitamin D synthesis, while other studies have examined the association between dietary supplementation and vitamin D levels in different oncologic indications. In certain oncologic types, low levels of vitamin D correlate with a higher risk of cancer progression or poorer outcomes. On the contrary, the protective role of vitamin D remains ambiguous for some cancers. Given that the majority of cancer patients exhibit vitamin D deficiency or insufficiency, there have been suggestions to adopt supplementation strategies. However, vitamin D modulates and interacts with several molecular pathways. Therefore, it is crucial to contextualize the level and circumstances in which the action of vitamin D is observed. Distinct outcomes may emerge based on factors such as the method of assessing vitamin D levels, the size of the study populations, their genetic background, and the specific cancer type under investigation. In this article, we summarize some of the relevant studies examining the relationship between vitamin D levels and cancer. We further briefly outline the process of vitamin D synthesis and its effects on specific cellular pathways involved in cancer progression, highlighting essential considerations for future vitamin D assessments and supplementation approaches.

Preeclampsia (PE), the most severe presentation of hypertensive disorders of pregnancy, is the major cause of morbidity and mortality linked to pregnancy, affecting both mother and fetus. Despite advances in prophylaxis and managing PE, delivery of the fetus remains the only causative treatment available. Focus on complex pathophysiology brought the potential for new treatment options, and more conservative options allowing reduction of feto-maternal complications and sequelae are being investigated. Endogenous digitalis-like factors, which have been linked to the pathogenesis of preeclampsia since the mid-1980s, have been shown to play a role in the pathogenesis of various cardiovascular diseases, including congestive heart failure and chronic renal disease. Elevated levels of EDLF have been described in pregnancy complicated by hypertensive disorders and are currently being investigated as a therapeutic target in the context of a possible breakthrough in managing preeclampsia. This review summarizes mechanisms implicating EDLFs in the pathogenesis of preeclampsia and evidence for their potential role in treating this doubly life-threatening disease. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called advanced pulmonary sarcoidosis, APS) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetic factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic characteristics and molecular pathways which are believed to be associated with the development of APS. [ABSTRACT FROM AUTHOR]

Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy—namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories—clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets—and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features. Methods: H-RAS, C-RAF, MAPK1, MAPK2, and ERK were quantified through ELISA, and genetic polymorphisms were evaluated through real-time PCR. Results: We prospectively recruited 201 individuals (158 positive and 43 negative for SARS-CoV-2): 35 were male, and their median age was 65 years. MAPK-related biomarker levels were increased in SARS-CoV-2-positive participants (n = 89) compared to negative ones (n = 29). Dyspnea was reported by 48%; this symptom was associated with PBMC C-RAF levels in positive participants (p = 0.022) and type of ventilation (p = 0.031). The highest degree of ventilation was used by 8% for invasive ventilation and 41% for continuous positive airway pressure (CPAP). Conclusions: This is the first study that showed a possible contribution of MAPK-related biomarkers in affecting COVID-19 clinical features, and this may be relevant for identifying COVID-19 positive participants at risk of serious complications. [ABSTRACT FROM AUTHOR]

Abstract Background Urothelial carcinomas (UC) can be either in the upper or in the lower urinary tract or both. Urothelial bladder cancer (UBC) is more common than upper tract urothelial carcinoma (UTUC). This research was designed to study the difference between UBC and UTUC using the molecular pathways including (MAPK/ERK) pathway, cell cycle regulating genes, and oncogenic genes. Methods To study the discrepancy between UBC and UTUC, a prospective trial was carried out for 31 radical cystectomy and 19 nephrouretrectomy fresh-frozen specimens of UBC and UTUC patients, respectively. The expression level of mRNA of eight genes namely EGFR, ELK1, c-fos, survivin, TP53, RB1, FGFR3, and hTERT was assessed in normal adjacent tissues, UTUC, and UBC by RT-PCR. Results Comparison between UTUC and UBC regarding the expression level of mRNA of the EGFR, ELK1, c-fos, survivin, TP53, and FGFR3 had significant difference (p-value < 0.001), while the expression level of RB1 and hTERT level had no significance. Sensitivity/specificity of EGFR, Elk1, c-fos, survivin, TP53, and FGFR3 was 0.78/0.90, 0.84/0.90, 0.84/0.80, 0.84/0.96, 0.94/0.93, and 0.89/0.93, respectively, to differentiate between UTUC and UBC. Conclusions Despite the fact that UTUC and UBC share the same origin, there is a clear evidence that there is a molecular difference between them. This molecular difference could be the reason that UTUC is more aggressive than UBC.

Nuclear receptor 4A1 (NR4A1), a member of the NR4A subfamily, acts as a gene regulator in a wide range of signaling pathways and responses to human diseases. Here, we provide a brief overview of the current functions of NR4A1 in human diseases and the factors involved in its function. A deeper understanding of these mechanisms can potentially improve drug development and disease therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most common cancer among women worldwide. Although many recommendations on the screening, diagnosis, and treatment of cervical cancer have been established, no comprehensive molecular mechanism for cervical cancer has been determined. Hence, this systematic review and integrated bioinformatic analysis provides new insight into the key genes and pathways involved in the pathogenesis of cervical cancer and, thus, can be beneficial for developing better screening and treatment strategies for cervical cancer. Cervical cancer is the leading cause of cancer-related death among women in developing countries. However, no comprehensive molecular mechanism for cervical cancer has been established, as many studies were small-cohort studies conducted with small sample sizes. A thorough literature search was performed using the PubMed, Scopus, EBSCOhost, and Science Direct databases. Medical Subject Heading (MeSH) terms such as "Uterine Cervical Neoplasms" and "gene expression" were used as the keywords in all fields. A total of 4027 studies were retrieved, and only clinical studies, which used the microarray method to identify differentially expressed genes (DEGs) in the cervical tissue of cervical cancer patients, were selected. Following the screening, 6 studies were selected and 1128 DEGs were extracted from the data. Sixty-two differentially expressed genes from at least two studies were selected for further analysis by DAVID, STRING, and Cytoscape software. In cervical cancer pathogenesis, three significant clusters with high intermolecular interactions from the Protein–Protein Interaction (PPI) network complex revealed three major molecular mechanisms, including cell signaling, cell cycle, and cell differentiation. Subsequently, eight genes were chosen as the candidate genes based on their involvement in the relevant gene ontology (GO) and their interaction with other genes in the PPI network through undirected first neighbor nodes. The present systematic review improves our understanding of the molecular mechanism of cervical cancer and the proposed genes that can be used to expand the biomarker panel in the screening for cervical cancer. The targeted genes may be beneficial for the development of better treatment strategies. [ABSTRACT FROM AUTHOR]

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a distinct subtype of T-cell non-Hodgkin lymphoma that arises in the context of prolonged exposure to textured breast implants. The intent of this manuscript is to explore whether the bacterial presence in biofilms on these implants is a mere incidental finding or plays a pivotal role in the pathogenesis of BIA-ALCL. Our goal is to delineate the extent of bacterial involvement, offering insights into potential underlying mechanisms, and establishing future research priorities aimed at resolving the remaining uncertainties surrounding this complex association. A comprehensive systematic review of several databases was performed. The search strategy was designed and conducted by an experienced librarian using controlled vocabulary with keywords. The electronic search identified 442 publications. After evaluation, six studies from 2015 to 2021 were included, encompassing 201 female patients aged 23 to 75. The diagnosis span post-implantation ranged from 53 to 135.6 months. Studies consistently found bacteria near breast implants in both BIA-ALCL cases and controls, with varied microbial findings. Both BIA-ALCL cases and controls exhibited the presence of specific bacteria, including Pseudomonas aeruginosa, Klebsiella oxytoca, Staphylococcus aureus, and Ralstonia spp., without any statistically significant differences between groups. The use of antiseptic and antimicrobial agents during implant insertion did not demonstrate any impact on reducing or altering the risk of developing BIA-ALCL. Our systematic review reveals that the current evidence is inadequate to link bacterial etiology as a central factor in the development of BIA-ALCL. The limitations in the existing data prevent a complete dismissal of the role of biofilms in its pathogenesis. The observed gap in knowledge underscores the need for more focused and comprehensive research, which should be structured in a multi-faceted approach. Initially, this involves the utilization of sophisticated genomic and proteomic methods. Following this, it is crucial to delve into the study of immunological reactions specifically induced by biofilms. Finally, this research should incorporate extended observational studies, meticulously tracking the evolution of biofilm development and its correlation with the emergence of BIA-ALCL. In light of the inconclusive nature of current findings, further investigation is not only justified but urgently needed to clarify these unresolved issues.

Diabetic retinopathy (DR) is one of the most common complications of diabetes and major cause of blindness among people over 50 years old. Current studies showed that the vascular endothelial growth factor (VEGF) played a central role in the pathogenesis of DR, and application of anti-VEGF has been widely acknowledged in treatment of DR targeting retinal neovascularization. However, anti-VEGF therapy has several limitations such as drug resistance. It is essential to develop new drugs for future clinical practice. The vitreous takes up 80% of the whole globe volume and is in direct contact with the retina, making it possible to explore the pathogenesis of DR by studying related factors in the vitreous. This article reviewed recent studies on DR-related factors in the vitreous, elaborating the VEGF upstream hypoxia-inducible factor (HIF) pathway and downstream pathways phosphatidylinositol diphosphate (PIP2), phosphoinositide-3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways. Moreover, factors other than VEGF contributing to the pathogenesis of DR in the vitreous were also summarized, which included factors in four major systems, kallikrein-kinin system such as bradykinin, plasma kallikrein, and coagulation factor XII, oxidative stress system such as lipid peroxide, and superoxide dismutase, inflammation-related factors such as interleukin-1β/6/13/37, and interferon-γ, matrix metalloproteinase (MMP) system such as MMP-9/14. Additionally, we also introduced other DR-related factors such as adiponectin, certain specific amino acids, non-coding RNA and renin (pro) receptor in separate studies.

Berberine is a metabolite of many medicinal plants. Chemically, berberine belongs to the isoquinoline alkaloids family. The roots of plants grown at lower elevations have a higher concentration of berberine as compared to plants grown at higher elevations. Berberine is a natural substance, which is now among the patent pharmaceuticals for reducing chronic disorders and malignancies. Berberine is also classified as a nutraceutical. Nutraceuticals have been associated with various health benefits via modifying microRNA (miR) expression systems, apoptosis, gene activity, chemical signals/pathways and activation of transcription factors thus aiding in the prevention from various ailments. The pharmacokinetic studies revealed that berberine is poorly absorbed via intestinal walls therefore, its concentration level is extremely low in body fluid. However, the quantity of berberine and its active derivatives in organs is higher as compared to blood as it stably present in tissues. Berberine has an effective role in the body as an anticancer, antidiabetic, antiobesity, antioxidant, antiinflammatory, neuroprotective, hepatoprotective, antiaging and cardioprotective agent. In this review, the therapeutic potentials of berberine are discussed to understand its nutraceutical importance. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos. Moreover, few literature reviews have been conducted with these studies. The aim of this systematic review is to evaluate the molecular mechanisms of ZIKV teratogenesis determined from studies in animal models. PubMed/MEDLINE, EMBASE, Web of Science, and Scopus as well as grey literature were searched for studies that evaluated molecular alterations related to ZIKV teratogenesis which occurred during embryonic development. Nine studies were included: six with mice, one with mice and guinea pigs, one with pigs and one with chickens. In general, studies presented an unclear or high risk of bias for methodological criteria. Most of studies reported embryos exposed to ZIKV presenting microcephaly, reduced cortex thickness, and growth restriction. Different techniques were used to evaluated molecular changes in the animals following ZIKV infection: RNA sequencing, RT-qPCR, and in situ hybridization. It was found that common pathways are changed in most studies, being pathways related to immune response upregulated and those involved to neurodevelopment downregulated. [ABSTRACT FROM AUTHOR]

In China, the Cranoglanis bouderius is classified as a national class II-protected animal. The development of C. bouderius populations has been affected by a variety of factors over the past few decades, with severe declines occurring. Considering the likelihood of continued population declines of the C. bouderius in the future, it is critical to investigate the currently unknown characteristics of gonadal differentiation and sex-related genes for C. bouderius conservation. In this study, the Illumina sequencing platform was used to sequence the gonadal transcriptome of the C. bouderius to identify the pathways and genes related to gonadal development and analyze the expression differences in the gonads. A total of 12,002 DEGs were identified, with 7220 being significantly expressed in the ovary and 4782 being significantly expressed in the testis. According to the functional enrichment results, the cell cycle, RNA transport, apoptosis, Wnt signaling pathway, p53 signaling pathway, and prolactin signaling pathway play important roles in sex development in the C. bouderius. Furthermore, the sequence characterization and evolutionary analysis revealed that AMH, DAX1, NANOS1, and AR of the C. bouderius are highly conserved. Specifically, the qRT-PCR results from various tissues showed significant differences in AMH, DAX1, NANOS1, and AR expression levels in the gonads of both sexes of C. bouderius. These analyses indicated that AMH, DAX1, NANOS1, and AR may play important roles in the differentiation and development of C. bouderius gonads. To our best knowledge, this study is the first to analyze the C. bouderius gonadal transcriptome and identify the structures of sex-related genes, laying the foundation for future research. [ABSTRACT FROM AUTHOR]

Glioma is characterized as the most aggressive brain tumor that occurred in the central nervous system. The circadian rhythm is an essential cyclic change system generated by the endogenous circadian clock. Current studies found that the circadian clock affects glioma pathophysiology. It is still controversial whether the circadian rhythm disruption is a cause or an effect of tumorigenesis. This review discussed the association between cell cycle and circadian clock and provided a prominent molecular theoretical basis for tumor therapy. We illustrated the external factors affecting the circadian clock including thermodynamics, hypoxia, post‐translation, and microRNA, while the internal characteristics concerning the circadian clock in glioma involve stemness, metabolism, radiotherapy sensitivity, and chemotherapy sensitivity. We also summarized the molecular pathways and the therapeutic drugs involved in the glioma circadian rhythm. There are still many questions in this field waiting for further investigation. The results of glioma chronotherapy in sensitizing radiation therapy and chemotherapy have shown great therapeutic potential in improving clinical outcomes. These findings will help us further understand the characteristics of glioma pathophysiology. [ABSTRACT FROM AUTHOR]

The ovary is commonly known as an endocrine gland responsible for sex steroid production. One of the outstanding cells in ovarian microenvironment - granulosa cells (GCs) are responsible for converting the androgens to estrogens during follicular growth and secreting progesterone after ovulation. These secretory processes within the ovary are directly involved in hormonal signaling pathways, and they depend on different stages of cholesterol and lipid biosynthesis during the ovarian cycle. The understating of the regulation and further investigation into the processes taking part in ovary will expose new clinical advantages in detection and treatment of female reproductive system diseases associated with sex hormone abnormalities. The expression of genes belonging to ontology groups associated with steroid biosynthesis and metabolism, such as "cholesterol biosynthetic process" (GO:0006695, "regulation of lipid biosynthetic process" (GO:0046890), "regulation of lipid metabolic process" (GO:0019216), "response to insulin" (GO:0032868) and "response to lipopolysaccharide" (GO:0032496) were analyzed by using the microarray approach. The patterns of gene expression in human GCs at days 1-day, 7-day, 15-day, and 30-day of primary in vitro culture have been analyzed. Based on the microarray results, a group of upregulated genes have been selected: CCL20, CXCL5, STAR, MSMO1, and AADAC. The genes STAT5B, OPA3, PPARG, PROX1, and SEC14L2 were decreased across all the experimental groups during the 30-day cell cultivation period. These results suggest that, the GCs in cell culture under in vitro express steroidogenic markers and it is important to understand associations with lipid and liposaccharide synthesis relative to reproductive medicine. [ABSTRACT FROM AUTHOR]

Background: Urothelial carcinomas (UC) can be either in the upper or in the lower urinary tract or both. Urothelial bladder cancer (UBC) is more common than upper tract urothelial carcinoma (UTUC). This research was designed to study the difference between UBC and UTUC using the molecular pathways including (MAPK/ERK) pathway, cell cycle regulating genes, and oncogenic genes. Methods: To study the discrepancy between UBC and UTUC, a prospective trial was carried out for 31 radical cystectomy and 19 nephrouretrectomy fresh-frozen specimens of UBC and UTUC patients, respectively. The expression level of mRNA of eight genes namely EGFR, ELK1, c-fos, survivin, TP53, RB1, FGFR3, and hTERT was assessed in normal adjacent tissues, UTUC, and UBC by RT-PCR. Results: Comparison between UTUC and UBC regarding the expression level of mRNA of the EGFR, ELK1, c-fos, survivin, TP53, and FGFR3 had significant difference (p-value < 0.001), while the expression level of RB1 and hTERT level had no significance. Sensitivity/specificity of EGFR, Elk1, c-fos, survivin, TP53, and FGFR3 was 0.78/0.90, 0.84/0.90, 0.84/0.80, 0.84/0.96, 0.94/0.93, and 0.89/0.93, respectively, to differentiate between UTUC and UBC. Conclusions: Despite the fact that UTUC and UBC share the same origin, there is a clear evidence that there is a molecular difference between them. This molecular difference could be the reason that UTUC is more aggressive than UBC. [ABSTRACT FROM AUTHOR]

Pyogenic bacteria are associated with a wide range of clinical manifestations, ranging from common and relatively mild respiratory and cutaneous infections to life-threatening localized or systemic infections, such as sepsis and profound abscesses. Despite vaccination and the widespread use of effective antibiotic treatment, severe infection is still observed in a subset of affected patients. We aim to summarize the available data regarding inborn errors of immunity that result in a high risk of severe pyogenic infections. Case series, as well as review and original articles on human genetic susceptibility to pyogenic infections were examined. We review host-associated factors resulting in inborn errors of immunity and leading to a susceptibility to pyogenic infections, including deficiency in major components of the immune system (e.g., neutrophils, complement, immunoglobulin, and spleen function) and novel monogenic disorders resulting in specific susceptibility to pyogenic infection. Specifically, innate immune system deficiency involving toll-like receptors and associated signaling typically predispose to a narrow spectrum of bacterial diseases in otherwise healthy people, making a diagnosis more difficult to suspect and confirm. More complex syndromes, such as hyper IgE syndrome, are associated with a high risk of pyogenic infections due to an impairment of the interleukin-6 or -17 signaling, demonstrating the pivotal role of these pathways in controlling bacterial infections. In clinical practice, awareness of such conditions is essential, especially in the pediatric setting, to avoid a potentially fatal diagnostic delay, set the most proper and prompt treatment, and ensure prevention of severe complications. [ABSTRACT FROM AUTHOR]