Cannabis is a commonly used recreational and therapeutic substance in our society. There are a variety of established physical, social, and mental health impacts associated with cannabis use. However, there is no overview of the impact cannabis use has on the genitourinary system. Thus, this scoping review aims to present data on the impact of cannabis on the genitourinary system.

A scoping review search was undertaken on Embase, Medline, and Web of Science. There were no date restrictions applied. Studies that included data from humans, exposure to cannabis, and outcomes related to the genitourinary system were included. Opinion pieces, commentaries, perspectives, and studies not available in English were excluded.

A total of 50 articles met this review’s inclusion criteria. The various studies were thematically organized into four themes: adverse outcomes related to cancer (n = 4), non-cancerous urogenital illness (n = 31), kidney transplant (n = 4), and therapeutic use of cannabis (n = 11). There were several non-cancerous urogenital illnesses associated with cannabis use, including acute kidney injury, urinary retention, rhabdomyolysis, and renal infarcts. The data found in this review suggest that cannabis use may not be a contraindication to receiving a kidney transplant. Finally, several studies highlighted some of the therapeutic applications cannabis may have on the genitourinary system.

This review brings forward conflicting findings on the association between cannabis use and genitourinary malignancies. Moving forward, data from well-designed long-term research studies are needed to understand the impact cannabis use has on the genitourinary system.

Liver iron overload can induce hepatic expression of bone morphogenic protein (BMP) 6 and activate the BMP/SMAD pathway. However, serum iron overload can also activate SMAD but does not induce BMP6 expression. Therefore, the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain unclear. This study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD pathway.

A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin (Holo-Tf). A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 days. Western blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of hepcidin.

Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to BMP6. The E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression; specifically, SMURF1 expression dramatically decreased when the serum iron concentration was increased. Additionally, the expression of SMURF1 substrates, which are important molecules involved in the transduction of BMP/SMAD signaling, was significantly upregulated. Furthermore, in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron overload.

SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.

The results of new randomized clinical trials show that immunotherapy is the preferred treatment for a small proportion of metastatic colorectal cancers (mCRCs). For microsatellite instability-high mCRC, pembrolizumab, nivolumab, and ipilimumab are currently authorized as first- and second-line immune checkpoint agents. However, the problem concerns tumors with microsatellite stability where the “cold” microenvironment does not allow immunotherapy to function properly. All efforts are now aimed at ensuring that this microenvironment is inflamed and “hot”. In this review, we examine recent studies on immunotherapy for mCRC and assess novel drivers of immunotherapy response.

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy” nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA (mRNA) metabolism, showcasing the power of our approach. We investigate (1) mRNA translation in prokaryotes and eukaryotes, (2) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (3) microRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (4) identification of disrupted sequences that could lead to potential illnesses. To achieve this, we used: (a) infinite (finitely generated) groups fp, with generators representing the r + 1 distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly (A) tail in item (ii), and the microRNA seed in item (iii)]; (b) aperiodicity theory, which connects healthy groups fp to free groups Fr of rank r and their profinite completion F ^ r , and (c) the representation theory of groups fp over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

Non-alcoholic fatty liver disease (NAFLD) is an extremely prevalent disease, and the presence and severity of liver fibrosis are considered one of the most important factors determining its prognosis. Hepatic stellate cells (HSCs) are essential in hepatic fibrogenesis associated with NAFLD. A number of factors underlying NAFLD pathogenesis may promote HSCs activation, leading to the development of profibrotic and proinflammatory signs. In addition, for the fibrogenic transdifferentiation of quiescent HSCs, alterations in multiple genes are necessary, where epigenetic regulation plays a defining role. Epigenetic regulation induces changes in gene activity without altering the coding sequence, and these changes are stably inherited after the factor causing the alteration has disappeared. Epigenetic modifications comprise several regulatory mechanisms, including DNA methylation, covalent histone modification, chromatin remodeling, and non-coding RNAs. Since the mechanisms underlying epigenetic regulation of HSCs fibrogenic activation are reversible and dynamic, molecular targeted therapies aimed at correcting these mechanisms provide promising prospects for novel therapeutic approaches for treating liver fibrosis associated with NAFLD.

The impact of the characteristics of extrahepatic organ failure (EHOF) including the onset time, number, type, and sequence on the prognosis of acute-on-chronic liver failure (ACLF) patients remains unknown. This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients.

ACLF subjects enrolled at six hospitals in China were included in the analysis. The risk of mortality based on the characteristics of EHOF was evaluated. Survival of study groups was compared by Kaplan–Meier analysis and log-rank tests.

A total of 736 patients with ACLF were included. EHOF was observed in 402 patients (54.6%), of which 295 (73.4%) developed single EHOF (SEHOF) and 107 (26.6%) developed multiple EHOF (MEHOF). The most commonly observed EHOF was coagulation failure (47.0%), followed by renal (13.0%), brain (4.9%), respiratory (4.3%), and circulatory (2.3%) failure. Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis. However, no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis. Patients were further divided into three risk subgroups by the EHOF characteristics. Kaplan–Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts.

The mortality of ACLF patients was determined by the number and type, but not the onset time and sequence of EHOF. Risk stratification applicable to clinical practice was established.

Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children’s liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

Sarcopenia is a well-known complication of chronic liver disease (CLD), and it is almost always observed in patients with cirrhosis, at least in those with decompensated disease. Since nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is becoming the leading cause of end-stage liver disease, a new scenario characterized by the frequent coexistence of NAFLD, obesity, and sarcopenia is emerging. Although it is not yet resolved whether the bidirectional relationship between sarcopenia and NAFLD subtends causal determinants, it is clear that the interaction of these two conditions is associated with an increased risk of poor outcomes. Notably, during the course of CLD, deregulation of the liver-muscle-adipose tissue axis has been described. Unfortunately, owing to the lack of properly designed studies, specific therapeutic guidelines for patients with sarcopenia in the context of NAFLD-related CLD have not yet been defined. Strategies aimed to induce the loss of fat mass together with the maintenance of lean body mass seem most appropriate. This can be achieved by properly designed diets integrated with specific nutritional supplementations and accompanied by adequate physical exercise. Future studies aiming to add to the knowledge of the correct assessment and approach to sarcopenia in the context of NAFLD-related CLD are eagerly awaited.

Hepatic lipid homeostasis is not only essential for maintaining normal cellular and systemic metabolic function but is also closely related to the steatosis of the liver. The controversy over the nomenclature of non-alcoholic fatty liver disease (NAFLD) in the past three years has once again sparked in-depth discussions on the pathogenesis of this disease and its impact on systemic metabolism. Pituitary-targeted gland axes (PTGA), an important hormone-regulating system, are indispensable in lipid homeostasis. This review focuses on the roles of thyroid hormones, adrenal hormones, sex hormones, and their receptors in hepatic lipid homeostasis, and summarizes recent research on pituitary target gland axes-related drugs regulating hepatic lipid metabolism. It also calls on researchers and clinicians to recognize the concept of endocrine-associated fatty liver disease (EAFLD) and to re-examine human lipid metabolism from the macroscopic perspective of homeostatic balance.

China accounts for 14.9% of total cirrhosis deaths worldwide. A detailed and comprehensive understanding of the contemporary status of cirrhosis mortality in China is crucial for establishing strategies for intervention and decreasing the disease burden of cirrhosis worldwide. The study aimed to report the cirrhosis mortality rates in our whole country or province over time.

Mortality data from 2008 to 2020 were retrieved from the Disease Surveillance Point System (DSPs) of the Chinese Center for Disease Control and Prevention. The crude mortality rate and age-standardized mortality rate of patients with cirrhosis were stratified by sex, residential location, and region. The average annual percentage change (AAPC) in cirrhosis mortality rates from 2008 to 2020 was also calculated.

The crude mortality rate of cirrhosis was 4.57/100,000 people in 2020. Compared with females and individuals living in urban areas, males and people living in rural areas had greater age-standardized mortality. The crude mortality rate and age-standardized mortality rate in provinces in Southwest China (Guangxi, Yunnan, Guizhou, and Qinghai) were greater than those in other provinces. Moreover, with increasing age, the age-specific mortality rate increased significantly. From 2008 to 2020, the mortality rate of cirrhosis in China decreased except for in males aged 50–59 years, females aged 45–49 years and females aged 80–84 years.

The mortality rate of patients with cirrhosis in China decreased from 2008 to 2020. In the future, interventions of cirrhosis mortality control need to pay more attention to all males, females aged 45–49 and 80–84 years, and people living in rural areas and in provinces in Southwest China.

Infectious diseases caused by pathogenic strains of bacteria are a global cause of morbidity and mortality. Hospital-acquired infections caused by Klebsiella pneumonia and Pseudomonas aeruginosa were found vulnerable during the COVID-19 pandemic. They are also responsible for the onset of certain life-threatening infectious diseases such as cystic fibrosis, endocarditis, bacteremia, and sepsis. Looking into the importance of these two superbugs there is a strong need for extensive comparative differential gene expression analysis among the wild-type and mutant for betterment of intensive care unit patients especially as such pathogenic bacterial strains have a dangerous role in the intensive care unit.

This study revealed the RNA microarray gene expression profiles of GSE24688, GSE4026, and GSE117438. The study compared all genes from three different datasets and all drug resistance genes from two divergent organisms, Klebsiella pneumonia and Pseudomonas aeruginosa.

10 numbers of shared significant genes and five drug resistance genes were obtained in this study. These putative genes may show intriguing patterns of connection with resistance mechanisms and can be used in the field of diagnostics and treatment. Our divergent analysis also revealed a very clear distinct relation between Klebsiella pneumoniae and Pseudomonas aeruginosa at the genetic level, though they both function under antimicrobial resistance.

This study enhances the understanding of the genetic basis, providing valuable knowledge for the development of new strategies to combat antibiotic resistance and enhance the efficacy of existing antibiotics.

Over time, the pursuit of unraveling the source and process of a regular cell’s conversion into cancer has resulted in diverse theories. These can be as diverse as considering cancer to be a supernatural ailment or comprehending the complex dynamics found within specific cancer subtypes, where several biological challenges must be addressed. Several validated screening methods are scarce for many types of cancer, and the existing ones have their limitations. This often results in low patient adherence and unnecessary medical procedures, increasing the financial burden on healthcare systems. Consequently, there is a pressing demand for inventive, precise, and less intrusive instruments for detecting cancer at an early stage. In recent times, multicancer early detection (MCED) tests have emerged as a promising approach. These tests utilize molecular analysis of tumor-related markers found in bodily fluids and incorporate artificial intelligence to simultaneously identify various cancer types and distinguish between them. Despite ongoing evaluation in numerous significant clinical trials, MCED tests may become clinically available soon without a standardized framework for assessing their performance and safety. Currently, it is only a few of them are available to doctors with different mechanisms to detect cancer but have not been approved by the Food and Drug Administration for the market. In this article, we aim to highlight the currently developed various strategies for MCED and the major factors that are preventing their clinical implementation.

The traditional definition of epigenetics encompasses all molecular pathways that affect how a genotype expresses itself on the way to a particular phenotype, with epigenetics serving as the interface between genotype and phenotype. Unlike genetic changes, which may have protracted, irreversible effects on health and the emergence of illnesses, epigenetic modifications are reversible and do not change the DNA sequence. However, they can affect how our bodies interpret DNA sequences. Gene expression regulated by epigenetics has emerged as a major contributing element to the etiology of many diseases over time and a crucial determinant of human health. One of the strongest arguments in support of gene expression controlled by epigenetics comes from the startling discovery that DNA methylation causes X-chromosome inactivation, which has been connected to several diseases. The intrinsic uterine environment, where the embryo and fetus grow and develop over time to become neonates is vulnerable to early epigenetic settings throughout development, affecting the offspring’s long-term health as well as their predisposition for different diseases. The epigenetic settings of germ cell development are influenced by environmental factors, which can result in transgenerational epigenetic effects. Therefore, in this article, we essentially provide a summary of the present level of understanding concerning the function of epigenetics regarding critical facets of human health, including in embryonic development and adulthood, with a particular emphasis on explaining the underlying diverse epigenetic mechanisms that regulate the onset of many human diseases, as well as cutting-edge technological tools used to study the human epigenome. Finally, we talk about the state of epigenetic therapies, which might be put to use in the treatment of a range of human diseases.

The high mortality rate in hepatocellular carcinoma (HCC) is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage, with surgical treatment options unavailable. Conversion therapy, which involves both locoregional and systemic treatments, has the potential to downstage tumors in selected patients with initially unresectable HCC, thereby making surgical treatment a possibility and potentially increasing long-term survival. To optimize the conversion rate, it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative effort. In this review article, we summarize the clinical experience and evidence for conversion therapy in patients with ‘potentially resectable’ HCC from four perspectives: 1) defining the target population for conversion therapy, 2) selecting the appropriate conversion strategy, placing emphasis on the utilization of combination therapy that exhibits a significant objective response rate, 3) determining the timing and urgency of surgical resection, 4) promoting the adoption of a multidisciplinary team model. The authors are optimistic that with the continuous progress in treatment and a deeper understanding of HCC, the success rate of HCC conversion therapy will increase, and the overall survival of HCC patients will be prolonged.

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

The T-cell acute lymphoblastic leukemia 1 (TAL-1) transcription factor is crucial for T-cell differentiation, but the ectopic expression in 30% of cases can disrupt normal differentiation, and promote cancer progression. This can be due to microRNA (miRNA) dysregulation or other oncogenes. The present study covers articles related to T-cell acute lymphoblastic leukemia (T-ALL), TAL-1 and miRNA, which were published in the English language from 1994 to 2023. After analyzing the research, it is evident that the TAL-1 overexpression is associated with alterations in several miRNAs, which encompass both those that suppress tumors, and those that stimulate cell growth. The interplay between TAL-1 and miRNAs exhibits diverse dynamics. For example, specific miRNAs, such as miR-223, interact with the TAL-1 gene promoter, resulting in its upregulation. In contrast, the miR-17-92 cluster indirectly influences the stability of the TAL-1 transcription complex. Typically, the interaction between TAL-1 and its associated miRNAs follows a unidirectional pattern, in which miRNAs that target TAL-1 are downregulated, leading to elevated TAL-1 levels. Nevertheless, TAL-1 exhibits a bidirectional relationship with miR-223, in which each positively affects the expression of the other. In addition, there is a cooperative interaction between miR-146-5b and TAL-1. Unlike miR-223, TAL-1 reduces the expression of miR-146-5b, thereby inhibiting tumor growth. Individuals with T-ALL, who experience disruptions in the TAL-1 and miRNA network, often face a poor prognosis, and their tumors tend to be larger. In conclusion, delving deeper into the network of miRNAs associated with TAL-1 in T-ALL offers a novel perspective on cancer prognosis and the development of improved diagnostic and treatment strategies.

Diabetes mellitus is a global health concern, and one of its most common complications is diabetic peripheral neuropathy (DPN). The vascular endothelial growth factor (VEGF) gene, which influences not only blood vessels but also neurons, has been studied in the occurrence of DPN. Polymorphism of the VEGF gene may affect the VEGF expression. This study aimed to identify, evaluate, and summarize all relevant studies about VEGF gene polymorphisms in DPN.

We performed a systematic review of the association of VEGF gene polymorphisms in patients with diabetic neuropathy based on a comprehensive search of PubMed, ScienceDirect, ProQuest, and EBSCOhost. A meta-analysis was performed on the most studied gene to clarify its association. Newcastle-Ottawa scale (NOS) was used to verify the quality of the evidence. Hardy-Weinberg equilibrium and six other items were used to determine whether the study was eligible for meta-analysis. Odds ratios and standardized mean differences with 95% confidence intervals were used to determine the association.

The systematic review included five case-control and three cross-sectional studies with six VEGF gene polymorphisms (VEGF 936C/T, VEGF −7C/T, VEGF −1001G/C, VEGF −1154G/A, VEGF −2678C/A, and VEGF 405G/C) and the final meta-analysis included four studies with a highly studied gene (VEGF 936C/T). Newcastle-Ottawa scale quality appraisal resulted in six good/high quality and two moderate quality studies. Meta-analysis showed that VEGF 936 C/T polymorphism was associated with a decreased risk of diabetic peripheral neuropathy (odd ratio 0.63; 95% confidence interval: 0.49–0.81; p = 0.0004).

Our meta-analysis suggests that the VEGF 936C/T gene polymorphism is linked to a decreased risk of diabetic peripheral neuropathy. This gene has the potential to be a predictive biomarker for determining who is at a lower risk of developing diabetic peripheral neuropathy. Early preventive efforts should be addressed in patients bearing the 936C allele.

Due to the increased demand for food for the growing population, pesticides are widely used to control diseases and boost productivity. This study was designed to evaluate the toxic effects of the fungicide, Mancozeb (MZ), in the liver of the fish strain Channa punctatus.

Fifty-four healthy C. punctatus fish (24 ± 4.0 g, 11.0 ± 2.0 cm) were divided into three groups (n = 18 per group): control, T1 (20% of 96 h-LC50 – 2.068 mg/L) and T2 (40% of 96 h-LC50 − 4.136 mg/L). Reactive oxygen species, redox imbalance, and liver biomarkers were measured after 20, 40, and 60 d of MZ exposure. Transcriptional profiling of XBP1s and NOX4 genes was performed after 60 d.

There were significant (p < 0.05) increases in reactive oxygen species induction, oxidative stress biomarkers (lactate dehydrogenase enzyme activity, glutathione peroxidase, superoxide dismutase and catalase), and liver biomarkers (alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin) after 20, 40, and 60 d of MZ exposure. However, there were significant (p < 0.05) decreases in superoxide dismutase and catalase after 40 d. There was a significant (p < 0.05) upregulation in XBP1s (5.1-fold) and NOX4 (3.3-fold) gene expression in the T2 group after 60 d. These results collectively evinces the inflammatory response triggered by MZ. It may serve as early bio-indicators of endoplasmic reticulum stress and in prevention and treatment of liver diseases.

The present study established that MZ is an oxidative stress inducer that may lead to liver diseases like liver steatohepatitis, non-alcoholic fatty liver disease, and non-alcoholic liver steatohepatitis. Further studies are required to elucidate the different mechanisms and signaling pathways that can minimize liver injury.

Breast cancer remains a significant global health concern, warranting further exploration into its genetic basis and potential therapeutic targets. This study aimed to elucidate the genetic associations of seven pivotal genes with breast cancer and discern their potential role in disease prognosis.

The genes VEGFA, BRCA1, RAD51, CCNB1, CHEK1, CDK1, and XRCC4 were curated from over 30 articles. Their association with breast cancer was analyzed using both in silico and in vitro techniques. The in silico assessment involved constructing a protein-protein interaction network, accompanied by Gene Ontology and pathway enrichment analysis. Further, survival and expression analysis were conducted using Kaplan-Meier Plotter and the UALCAN database respectively. At the protein level, expression was observed using the Human Protein Atlas database. The in vitro validation involved analyzing mRNA expression levels in 10 breast cancer tissue samples.

The study revealed that all seven genes are significantly upregulated in breast cancer tissues compared to normal tissues, highlighting their critical role in tumor development and progression. Protein-protein interaction analysis confirmed their central involvement in vital biological processes related to breast cancer. Survival analysis showed that high expressions of these genes are associated with poorer patient prognosis, with hazard ratios indicating their potential as prognostic markers. In vitro validation further supported their overexpression in breast cancer, suggesting their importance in molecular landscape of the disease and their value as targets for therapeutic intervention.

This study provides a profound understanding of the genetic landscape of breast cancer, emphasizing the significance of the selected seven genes in the pathology of the disease. These findings suggest potential avenues for therapeutic targeting and the advancement of personalized medicine in breast cancer treatment.