Cyclophosphamide (CP) is a potent chemotherapeutic agent utilized in the treatment of various types of cancer. However, in addition to its efficacy in combating cancer, CP also has severe side effects, including damage to male gonadal functions. This paper aims to explore the cytotoxic properties of CP and its mechanistic impacts on male gonadal functions. The search strategy was conducted using several reviewed articles indexed in PubMed, Science Direct, EBSCO, Scopus, Cochrane Library, Sage Journals, and Google Scholar. CP is an alkylating agent that damages cancer cell DNA, inhibiting growth and division. It also affects healthy cells, leading to severe cytotoxicity. In male gonadal tissues, CP damages germ cells, Leydig cells, and Sertoli cells, causing decreased sperm count, testosterone levels, and disruption of the blood-testis barrier. The metabolism of CP in the liver generates reactive oxygen species, leading to oxidative damage and cell death. Moreover, CP also affects the hypothalamic-pituitary-gonadal axis, regulating male gonadal functions. CP disrupts the production and secretion of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, resulting in a decrease in testosterone levels and impaired spermatogenesis. Additionally, CP exerts its cytotoxic effects by inhibiting the proliferation and differentiation of germ cells, leading to a decrease in sperm production. It also affects Leydig cells, which are responsible for the production of testosterone, thus decreasing testosterone levels. In conclusion, CP exhibits potent cytotoxic properties that not only affect cancer cells but also severely damage male gonadal functions. The mechanisms involved in CP-induced gonadal toxicity include oxidative stress and disruption of the hypothalamic-pituitary-gonadal axis. Therefore, it is crucial to consider the potential gonadal toxicity of CP when prescribing it for cancer treatment and to closely monitor the gonadal functions of male patients receiving CP therapy.

A key element in the pathogenesis of metabolic syndrome (MetS) is the reprogramming of hypothalamic cells at the genetic level (in the prenatal phase), which leads to neuroinflammation. We hypothesize that alterations in the structure of hypothalamic neurons mediated by (epi)genetic alterations are directly related to impaired expression/production of neurotrophins and neurotransmitters that control the metabolism of substances in the brain and periphery, including brain-derived neurotrophic factor (BDNF). The aim of this review is to describe the molecular genetic and epigenetic role of BDNF in the development of MetS. Articles entered into the National Library of Medicine Medline database via the PubMed interface were used to create this review. We attempted to include as much literature as possible, including reviews, animal studies, cell culture studies, and clinical trials. Studies on BDNF point to its role in metabolic processes, including glucose, insulin, and cholesterol homeostasis. Evidence-based studies show that multiple genes in close proximity to BDNF are involved in the development of MetS. Studies aimed at analyzing BDNF in metabolic diseases using different biological samples will reveal clear pathophysiological links between processes in the brain and in the periphery.

Fine needle aspiration cytology (FNAC) is a cost-efficient technique for the management of thyroid nodules. Changes in the World Health Organization classification of thyroid tumors can influence reliability of cytology. The 2023 Bethesda System for Reporting Thyroid Cytopathology has adapted cytological nomenclature to these changes. The aim of this paper was to analyze the management of atypia of undetermined significance (AUS) in our institution.

Retrospective review of thyroid FNAC diagnosed with AUS in a single hospital between 2014 and 2022. We analyzed the management of patients and the risk of malignancy associated with AUS.

AUS represented 7.5% of all thyroid FNAC diagnoses (273 patients). In 74.1% of the patients, FNAC was repeated, and 54.9% of the lesions were downgraded. Surgical resection of the nodule was performed in 38.2% of the patients, mostly after a repeat FNAC with upgrading. Ninety-one percent of the patients downgraded in the repeat FNAC did not undergo surgery. The risk of malignancy of the AUS category after repeat FNAC was 26.1%. AUS diagnosis was due to nuclear atypia in 32% of the patients, and we found a significant association between nuclear atypia and upgrading in repeat FNAC. Of the 96 patients who underwent surgery in our series, 42 had malignant lesions, including noninvasive follicular thyroid neoplasms with papillary-like features.

The clinical management of AUS patients includes repeat FNAC, which is strongly correlated with the risk of malignancy. Nuclear atypia seems to be more predictive of malignancy than architectural patterns.

Acute liver failure (ALF) is a life-threatening clinical problem with limited treatment options. Administration of human umbilical cord mesenchymal stem cells (hUC-MSCs) may be a promising approach for ALF. This study aimed to explore the role of hUC-MSCs in the treatment of ALF and the underlying mechanisms.

A mouse model of ALF was induced by lipopolysaccharide and d-galactosamine administration. The therapeutic effects of hUC-MSCs were evaluated by assessing serum enzyme activity, histological appearance, and cell apoptosis in liver tissues. The apoptosis rate was analyzed in AML12 cells. The levels of inflammatory cytokines and the phenotype of RAW264.7 cells co-cultured with hUC-MSCs were detected. The C-Jun N-terminal kinase/nuclear factor-kappa B signaling pathway was studied.

The hUC-MSCs treatment decreased the levels of serum alanine aminotransferase and aspartate aminotransferase, reduced pathological damage, alleviated hepatocyte apoptosis, and reduced mortality in vivo. The hUC-MSCs co-culture reduced the apoptosis rate of AML12 cells in vitro. Moreover, lipopolysaccharide-stimulated RAW264.7 cells had higher levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β and showed more CD86-positive cells, whereas the hUC-MSCs co-culture reduced the levels of the three inflammatory cytokines and increased the ratio of CD206-positive cells. The hUC-MSCs treatment inhibited the activation of phosphorylated (p)-C-Jun N-terminal kinase and p-nuclear factor-kappa B not only in liver tissues but also in AML12 and RAW264.7 cells co-cultured with hUC-MSCs.

hUC-MSCs could alleviate ALF by regulating hepatocyte apoptosis and macrophage polarization, thus hUC-MSC-based cell therapy may be an alternative option for patients with ALF.

Hepatocellular carcinoma (HCC) is a prominent contributor to cancer-related mortality worldwide. Early detection and diagnosis of liver cancer can significantly improve its prognosis and patient survival. Ultrasound technology, serving has undergone substantial advances as the primary method of HCC surveillance and has broadened its scope in recent years for effective management of HCC. This article is a comprehensive overview of ultrasound technology in the treatment of HCC, encompassing early detection, diagnosis, staging, treatment evaluation, and prognostic assessment. In addition, the authors summarized the application of contrast-enhanced ultrasound in the diagnosis of HCC and assessment of prognosis. Finally, the authors discussed further directions in this field by emphasizing overcoming existing obstacles and integrating cutting-edge technologies.

Restenosis is a serious complication for patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). In this prospective clinical study, we aimed to investigate the effects of Radix Salviae decoction (RSD) on coronary stenosis and restenosis in CHD patients.

We conducted this study at Guangdong Hospital of Traditional Chinese Medicine (registration No. BF2022-052) and enrolled 60 patients diagnosed with CHD for PCI surgery. The patients were divided into a control group and an RSD treatment group of 30 cases each. The primary outcome was restenosis after PCI, and the secondary outcome was newly increased stenosis (neostenosis).

Fifty-eight of the 60 enrolled patients completed follow-up and were included in the final analysis, with 28 in the control and 30 in the RSD group. A baseline comparison of stenosis location, stenosis degree, and the number of vessels in stenosis before PCI showed comparable results (p > 0.05). Comparison of implanted stents showed similar features in stent diameter and stent length during PCI between the two groups (p > 0.05). For the primary outcome, there was no significant difference in restenosis percentage (p > 0.05) or the number of vessels in restenosis (p > 0.05) of the three arteries between groups. For the secondary outcome, neither the number of nonculprit vessels in neostenosis after PCI nor the percentage of neostenosis of the three arteries showed significant differences between groups (p > 0.05). Although multifactor logistic regression analysis for the incidence of restenosis did not find any statistically significant factors (p > 0.05), the diagnosis of MI/angina (p = 0.031), average stent length (p = 0.010), and alanine transaminase (p = 0.027) were found to be significantly associated with neostenosis occurrence. Safety index measurement indicated that RSD had a good safety profile in clinical treatment.

Although the addition of Radix Salviae decoction for a short period did not significantly change restenosis and neostenosis after PCI, the diagnosis of MI/angina, average stent length and aspartate aminotransferase levels were significantly associated with neostenosis occurrence. This pilot research will help to design future studies in investigating RSD effects on stenosis.

Hepatitis B virus (HBV) infection is a major risk factor for cirrhosis and liver cancer, and its treatment continues to be difficult. We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids. The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens (HBsAg and HBeAg, respectively) and to elucidate the underlying mechanism.

We used dopamine-treated HBV-infected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels. We analyzed interferon-stimulated gene 15 (ISG15) expression in dopamine-treated cells. We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels. We analyzed the expression of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway factors in dopamine-treated cells. We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA, HBsAg, and HBeAg expression. HBV virus was collected from HepAD38.7 cell culture medium.

Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines. ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells. Dopamine-treated cells activated the JAK/STAT pathway, which upregulated ISG15 expression. In the adeno-associated virus-HBV murine infection model, dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.

Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.

Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Antimicrobial resistance (AMR) poses a significant threat to public health in the 21st century, with bacteria such as Campylobacter jejuni (C. jejuni) exhibiting multidrug resistance due to the presence of AMR genes. Understanding the evolutionary patterns and functional relationships of these genes is crucial for addressing this issue effectively.

We conducted phylogenetic analysis to examine the evolution of AMR genes in C. jejuni. Additionally, we constructed and analyzed a gene interaction network comprising 39 functional relationships. Clustering analysis was employed to identify interconnected clusters associated with AMR processes. Functional enrichment analysis was performed to explore the involvement of cellular components, molecular functions, and biological processes.

Our analysis revealed two interconnected clusters (C1 and C2) closely associated with AMR processes. Furthermore, genes encoding ribosomal proteins (rplE, rplV, rplG, rplK, rplA, rplJ, rpsE, rplB, rpsL, and rpmA) were identified as hub genes within the gene interaction network. These genes interact frequently with their functional counterparts, indicating their significance in AMR mechanisms. Enriched Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted the importance of the ribosome pathway in understanding antibiotic resistance mechanisms in C. jejuni.

The findings of this study enhance our understanding of the molecular mechanisms underlying AMR in C. jejuni. By elucidating the evolutionary patterns, gene interactions, and pathway enrichment, our study provides valuable insights that may contribute to the development of novel treatments for illnesses caused by this pathogen.

Environmental factors such as heavy metals can influence the gene expression profiles that can lead to diseases. MicroRNAs (miRNAs) are primary regulatory molecules related to health and disease that are sensitive to environmental factors. Several studies have shown an association between environmental exposure to toxic metals such as cadmium (Cd) and disease risk. Growing knowledge has shown that heavy metal toxicity can manifest through miRNAs. Therefore, dysregulated miRNAs are proposed as potential biomarkers for monitoring chronic metal exposure. This review aimed to evaluate the effect of Cd on changes in miRNA expression. The databases of PubMed, Web of Science (ISI), Scopus, and Google Scholar were systematically searched for all previous relevant articles from 2000 up to 2022. The following medical subject headings were used: (microRNAs OR miRs) AND (Heavy Metals OR Cadmium OR Cd) AND (miRs profile OR miRs Expression). Searched articles were divided into the categories of in vitro, in vivo, and human studies. MiRNAs, widely used for biomarker discovery in Cd-induced diseases, are still being researched to use these genes for reliable biomarker discovery in addition to current diagnostic and prognostic approaches. As the functional effects of miRNAs are by their target proteins, it is important to analyze the expression levels of multiple potential target proteins to fully understand the role and mechanism of miRNAs in Cd-induced diseases. Therefore, further investigations are required to understand the regulatory mechanisms of miRNAs and to obtain novel biomarkers, and these findings will be used to develop early diagnostic approaches as well as new preventive methods and treatment options for Cd-induced diseases.

Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism.

First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharide-induced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance assessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.

The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum, which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway.

The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Iron overload is a significant complication commonly observed in individuals with β-thalassemia, resulting from enhanced iron absorption due to ineffective erythropoiesis and frequent blood transfusions. Iron overload can lead to severe tissue damage and organ dysfunction, significantly impacting the quality of life for those affected. Additionally, recent research indicates that iron overload may also adversely impact mitochondrial function, further exacerbating the pathophysiology of this disease. Excessive iron accumulation in mitochondria can impair the electron transport chain, reduce adenosine tri phosphate synthesis, and increase the generation of reactive oxygen species, resulting in elevated tissue damage and clinical complications. Emerging evidence suggests that specific mitochondrial DNA (mtDNA) mutations may further contribute to the severity of iron overload in β-thalassemia patients. Currently, the clinical management of iron overload in patients with β-thalassemia primarily relies on conventional iron chelation therapies, aiming to reduce iron burden and prevent tissue damage. However, cases involving mtDNA mutations introduce additional complexities, necessitating personalized treatment approaches. Advances in gene therapy and mitochondrial replacement strategies offer promising avenues for potential targeted interventions. This review provides a comprehensive overview of the mechanisms underlying iron overload in β-thalassemia and its association with mtDNA mutations. It discusses the clinical manifestations, diagnostic challenges, and current treatment options for managing iron overload, while also highlighting emerging research directions and potential therapeutic targets for improved patient care. Ultimately, a better understanding of the complex interplay between iron overload and mtDNA mutations in β-thalassemia will pave the way for innovative strategies to alleviate the disease burden.

After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.

All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed.

The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: −1.5%, (95% CI: −6.4 to −3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, −2.85 mL/min vs. −3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.

The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

Breast cancer (BC) is the type of cancer with the highest incidence and mortality rates in women in the world. In the treatment of this neoplasia, several therapies are applied, including radiotherapy, hormonal therapy, chemotherapy, and biological therapy. Although most patients respond to these types of therapy, some patients over time, develop resistance or eventually relapse. Considering the above, future therapeutic concepts in BC are being directed at individualization of therapy and escalation of treatment based on tumor biology through the use of gene therapy. In this regard, a new genomic engineering technology, called the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9), has acquired great importance in recent years, as a potential gene editing tool, extensively applied in human cancer research and cancer treatment. The aim of this review was to describe the advantages, limitations, and applications of CRISPR gene editing technology in BC treatment. Our review emphasizes the innovative facets and profound importance of CRISPR gene editing technology within the BC treatment landscape. Additionally, it provides valuable information to consider when evaluating the risks associated with the implementation of CRISPR-Cas9 technology in BC therapy.

Parkinson’s disease (PD) is a common neurodegenerative disorder with unclear molecular mechanisms. Noncoding RNAs, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been identified as critical regulators of gene expression. This study aimed to investigate the triple network of lncRNA-miRNA-mRNA, known as competing endogenous RNAs (ceRNAs), and to identify essential lncRNAs that regulate PD-related gene expression through their target miRNAs. The study also identified a common triple network between COVID-19 and PD that may contribute to exacerbating PD symptoms.

A bioinformatics approach was employed to construct a PD ceRNA network using common PD genes, miRNAs and lncRNAs with the highest interaction with their targets. Also, a PD-COVID-19 triple network was constructed by integrating PD network nodes into the COVID-19 network.

The PD ceRNA network comprised 34 nodes, including 12 lncRNAs, 16 miRNAs with interconnections and six mRNAs, some of which were related to COVID-19. The network showed parallel expression of the SNCA and PARK7 genes as well as the NEAT1 and MALAT1 lncRNAs in both PD and COVID-19.

This study provide insights into the molecular mechanisms underlying the worsening of symptoms in PD patients with COVID-19. The PD and COVID-19 ceRNA network indicates that coronavirus could worsen PD symptoms by altering the expression of some genes related to PD. Therefore, COVID-19 could dysregulate the common RNAs involved in PD through lncRNAs, miRNAs.

Patients with newly diagnosed prostate cancer (PCA) face the critical decision of whether to undergo treatment with curative intent (TCI, surgery or radiation) or conservative treatment on the background of a cancer where the potential for over-treatment and under-treatment is real. This study aimed to investigate the influence of cancer- and patient-related factors on the initial treatment decision for men with a new diagnosis of PCA and to evaluate treatment decisions against relevant guidelines.

This study undertook a retrospective audit of the clinical records of 545 men who were diagnosed with PCA at four Australian urology services. Age, comorbidities, and cancer-related factors were recorded, with patients divided into risk groups based on cancer factors.

Cancer risk stratification emerged as a primary determinant influencing individual treatment choices, with low-risk patients being more likely to have active surveillance and those classified as intermediate or high-risk being more likely to have TCI. Surgery was more commonly offered to younger patients and those with fewer comorbidities. While 80% of patients received guideline-concordant treatment, 20% were identified as being over-treated, receiving TCI despite limited life expectancy and/or high comorbidities.

Managing men diagnosed with PCA should avoid under-treatment in young, otherwise healthy individuals with aggressive cancer by offering TCI. Conversely, over-treatment (unnecessary treatment), especially in men with low-grade cancer or individuals with limited life expectancy due to significant comorbidities, should be avoided to prevent unnecessary treatment when competing causes are more likely to be fatal than prostate cancer.

Cervical cancer is a significant public health concern worldwide. Current screening approaches include Pap smears, human papillomavirus testing, visual inspections, and emerging molecular techniques, aimed at enhancing precision and accessibility. The landscape also includes the increasing prominence of self-sampling and telemedicine, which broaden the reach of screening services. Human papillomavirus vaccination programs targeting young girls have the potential to significantly reduce long-term risk. These evolving strategies are supported by global initiatives such as the World Health Organization’s Cervical Cancer Elimination Initiative, aiming to increase screening efforts and reduce the global impact of cervical cancer. The key findings of this study suggested that current methodologies for the detection and prevention of cervical cancer are a little beneficial and there is a pressing need to use advanced technologies such as highly sophisticated equipment integrated with artificial intelligence. In addition, the detection of cervical cancer screening provides insights into evolving methodologies, promising prospects, and nuanced challenges that must be addressed to prevent this condition in females worldwide. Looking forward, future cervical cancer screening involves further refinements in molecular testing, expanded vaccine coverage, and the integration of telehealth solutions, promising increased accessibility and improved early detection to overcome insightful challenges.

About 30% of lung cancer patients are accessible to targeted therapy or immunotherapy based on the current criteria. In this study, a novel gene cluster expression analysis was introduced with a goal to potentially expand the treatments to more patients based on the proposed criteria.

Selected gene expression omnibus data sets were downloaded, normalized, and analyzed. A univariate recurrence prediction model was built based on the receiver operating characteristic, for which an optimal cutoff was determined to set abnormality status, called the gene cluster expression index (GCEI). Recurrence and survival risks were calculated and compared between two subgroups indexed by the GCEI. Moreover, a combinatory GCEI was also introduced and its performance was analyzed for combined multiple cluster statuses.

The recurrence risks of the patient subgroups with abnormally expressed clusters with GCEI = 1 were much higher than for the corresponding normal subgroup with GCEI = 0. The higher risks ranged from 120–300% that of the corresponding lower-risk group.

The GCEI can be used to classify lung cancers with dramatically different recurrence risks and may be used to guide targeted therapy or immunotherapy for patients who are in a high-risk group but do not qualify for such treatment according to conventional companion tests.