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.

While the incidence rates of hepatocellular carcinoma (HCC) are increasing, there are limited comprehensive data on demographic-specific incidence and mortality trends in the USA. We aimed to evaluate recent trends in HCC incidence and mortality among different demographic groups in the USA.

Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control’s United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control’s National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted.

Between 2001 and 2020, there were 467,346 patients diagnosed with HCC (26.0% women), with increasing incidence in both sexes without significant difference (p=0.65). In younger adults (78,169 patients), the incidence decreased in men but not in women (AAPC difference=−2.39, p=0.002). This was seen in various racial and ethnic groups, mostly driven by early-stage tumors (AAPC difference=−2.65, p=0.02). There were 329,973 deaths attributed to HCC between 2000 and 2020 (28.4% women). In younger adults (43,093 deaths), mortality decreased in men at a greater rate than in women (AAPC difference=1.61, p=0.007). This was seen in various racial and ethnic groups, most notably in non-Hispanic American Indian/Alaska Natives (AAPC difference=−4.51, p=0.01).

Nationwide USA data, covering nearly all HCC cases, show an increasing incidence and mortality over the last two decades. In younger adults, there was a decreasing incidence in men but not in women, due to early-stage tumors. Mortality improved in younger men at a greater rate than in women, especially in Non-Hispanic American Indian/Alaska Natives. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in demographic-specific populations, especially younger women.

The consequences of the coronavirus disease 2019 (COVID-19) pandemic on the perceived workload of health care professionals and remaining mental symptomatology are becoming increasingly visible. Increasing waiting lists and workload and decreasing employee capacity in mental health services will contribute to the problem of health care availability. In several studies, many of the responding mental health care workers (MHCWs) reported stress-related complaints and depression. Moreover, more clients with complaints, as a direct and indirect result of the COVID-19 pandemic, requested mental health care. Support for mental health care staff is needed to prevent further escalation. These insights trigger an appeal to government and mental health institutions to take responsibility for protecting MHCWs. This requires the right decisions and investment in the prevention and mental health support for MHCWs! Preparing health care professionals for future challenges by focusing on interventions early in their career, which improve mental stability to enhance resilience, seems to be important to prioritize.

Tumor necrosis factor (TNF) superfamily member 15 (TNFSF15) may have the potential to control vascular homeostasis and inflammation. Through binding to death receptor 3 (TNFRSF25), TNFSF15 promotes T-cell activation, proliferation, and the generation of multiple cytokines. TNFSF15-TNFRSF25 signaling is essential for effective T-cell immune responses in T-cell-mediated autoimmune diseases. Our goal is to study the role of the (TNFSF15) rs4979462 gene variant and TNFSF15 serum levels in systemic lupus erythematosus (SLE) in Egyptian patients.

A total of 118 patients with SLE and 102 age- and sex-matched healthy control volunteers were genotyped for the TNFSF15 rs4979462 variant by polymerase chain reaction-restriction fragment length polymorphism and verified by direct sequencing. TNFSF15 serum levels were measured using an enzyme-linked immunosorbent assay.

Regarding the TNFSF15 rs4979462 gene variant, there was a significant increase in the frequencies of combined genotypes (CT + TT) and T-allele among female patients with SLE compared with the healthy female subjects (OR = 2.6, 95% CI = 1.1–6.3, p = 0.027; OR = 2.7, 95% CI = 1.2–6.3, p = 0.015, respectively). The T-variant was significantly associated with serositis and thrombotic manifestations (OR = 2.8, 95% CI = 1.1–7.1, p = 0.032; OR = 2.9, 95% CI = 1.1–7.8, p = 0.023, respectively). The median serum TNFSF15 concentration was significantly higher in patients with SLE compared to the healthy control group and was correlated with the disease activity (p = 0.023, 0.012, respectively).

The TNFSF15 rs4979462 gene variant increases the risk of SLE in female subjects and modulates the clinical outcome of the disease. TNFSF15 serum level could be a biological marker of SLE disease activity.

Colorectal cancer (CRC) is the third most common malignancy worldwide. The average age at diagnosis of CRC is around 70 years old. This study aimed to assess the prevalence of asymptomatic CRC and premalignant lesions in the colon in OSI Araba.

This study included individuals aged 50–69 who were admitted to OSI Araba Health Centers. It spanned from the start of CRC screening through fecal occult blood test immunological analysis in 2009 to the publication of the latest updated data in 2021.

An average of 90.98% of participants obtained a definitive result. Specifically, 31.71% were normal, 1.22% had relevant non-neoplastic pathology, 5.49% had non-neoplastic polyps, 15.93% had low-risk adenomas, 22.26% had medium-risk adenomas, 17.65% had high-risk adenomas and 5.02% had CRC.

CRC screening is an effective strategy for reducing incidence and mortality rates, preventing new cases, and minimizing disease burden in the future.

Neuroblastoma is a heterogeneous solid tumor that originates extracranially from neuroblasts. Previous research has demonstrated that miR-492 polymorphisms can contribute to cancer susceptibility. However, their specific involvement in susceptibility to neuroblastoma has yet to be fully clarified.

To address this question, we used the TaqMan method to genotype miR-492 rs2289030 G>C in a cohort of 402 neuroblastoma children and 473 control individuals from Jiangsu Province, China.

Our study showed that there was no significant association between miR-492 rs2289030 G>C and the risk of neuroblastoma in children, as assessed by combined odds ratios (ORs) and 95% confidence intervals (P > 0.05).

Further validation of these findings requires well-designed studies with large sample sizes.

Global deaths attributed to gastric cancer (GC) are increasing, yet our understanding of it remains limited. Recently, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics have provided important insights into the dissection of metastasis-related biological processes in subpopulations of cells in the GC tumor microenvironment, especially intratumoral cellular heterogeneity and cell-cell interactions. In this review, we discuss the mechanisms underlying GC metastasis and potential strategies for developing upcoming immunotherapies by combining advances in scRNA-seq and spatial transcriptomics.

Obesity is a complex disease resulting from excessive adipose tissue in the body, leading to various metabolic, mechanical, and psychological complications. The prevalence of obesity has increased exponentially in the past few decades to reach an epidemic proportion. Obesity can predispose to or aggravate the fatty liver. Metabolic dysfunction-associated fatty liver disease (MAFLD) represents fatty liver in individuals who are either overweight/obese, or have type 2 diabetes, or have normal weight with at least two metabolic risk factors. MAFLD pathogenesis is multifactorial and involves an interplay of genetics, lifestyle-related factors, gut dysbiosis, lipotoxicity, and oxidative stress. Besides hepatic complications, MAFLD also has systemic implications in the form of increased risk for various metabolic diseases, cardiovascular diseases, malignancies, and infectious diseases. If left untreated, MAFLD can progress to liver cirrhosis and end-stage liver disease. Many noninvasive strategies like serum-based markers and imaging help diagnose MAFLD at an early stage. Timely detection and appropriate intervention are crucial for preventing its progression to advanced liver disease and hepatocellular carcinoma. Though lifestyle modification remains the main pillar of management, with advances in the treatment of obesity, newer agents are being tried for patients with MAFLD. The current therapeutic strategies are limited, and future research is needed to identify the subset of patients with MAFLD who are at a higher risk of hepatic and systemic complications and to develop more effective and personalized therapies.