The incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.

Herpetic Epithelial Keratitis is characterized by a corneal dendritic lesion, and prolonged or recurrent medication such as acyclovir, raises the possibility of resistant strains, necessitating the search for new therapies. An 84-year-old woman, phototype III, reported severe discomfort in the left eye. The presence of a dendritic ulcer was confirmed. Acyclovir therapy (oral—1.6 g/day and topical—seven days) was initiated and replaced by famciclovir (oral–1.5 g/day—seven days; topical acyclovir discontinued). Every three months, a new recurrence occurred. Famciclovir treatment (seven days) was subsequently supplemented with L-lysine (3 g—loading dose + 500 mg/day per 30 days) with L-arginine intake control. After amino acid supplementation, the clinical signs of the active lesion were reduced compared to previous treatment. Furthermore, a longer interval between recurrences was observed until they ultimately stopped. The patient is controlling L-arginine intake. When necessary, L-lysine supplementation is associated. Additional investigation is needed on the proposed supplementary therapy for Herpetic Epithelial Keratitis, which could help reduce side effects and resistance to antiviral drugs. However, as documented in this case report, amino acid supplementation can be recommended for controlling herpesvirus infection with no risk of adverse effects

This article explores the significant improvements in manufacturing of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) enabled by the microgravity environment in orbiting space vehicles. mAbs, which are extensively incorporated into modern cancer treatments based on their ability to specifically target and kill tumor cells, traditionally require intravenous (IV) delivery. However, the inconvenience, potential risks of infection, and adverse systemic effects associated with IV administration have led to a move towards subcutaneous (SC) self-administration formulations. Current limitations hindering the development of SC injections are high viscosity and limited solubility of mAbs at high concentrations. The microgravity environment of space provides potential solutions to these challenges by promoting the formation of colloidal crystalline protein suspensions of low-viscosity and high concentration suitable for SC injection. Although conducting research and manufacturing in microgravity poses its own set of challenges, the benefits of improving the delivery, storage, and stability of mAbs are substantial. SpacePharma has developed novel, autonomous, remote-controlled, microfluidics-based lab-on-chip microgravity systems as a platform for the rapid screening and improved growth of crystallized monoclonal antibodies inside micron-size droplets. The advancements in this field have significant potential to improve patient care by enabling large-scale manufacturing of crystallized mAb therapies in the emerging space economy.

Pleomorphic adenoma is the most common benign tumor of the salivary glands. Histologically, it is characterized by the presence of both epithelial and mesenchymal elements and may contain various metaplastic changes. This paper reported a case of pleomorphic adenoma with extensive mucinous metaplasia, which is histologically very similar to mucoepi- dermoid carcinoma. Pleomorphic adenoma with extensive mucinous and squamous differentiation may be misdiagnosed as mucoepidermoid carcinoma. Immunohistochemistry was ineffective in differential diagnosis, and the diagnosis was confirmed by the absence of mastermind like transcriptional coactivator 2 (MAML2) translocation. The detection of MAML2 translocation can help avoid misdiagnosis of MEC in similar cases. Additionally, the published literature on metaplasia on pleomorphic adenoma was also reviewed and summarized.

Visualization of the spatiotemporal organization and dynamics of the genome in the nucleus is essential to elucidate how chromatin structure and nuclear function are intertwined. In the past, such studies were limited by the lack of appropriate tools. However, various imaging techniques now allow direct visualization of genomic loci in living cells. One of the main drivers behind this progress is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) technology. Initially used as an efficient and specific genome editing tool, the versatility of the CRISPR/Cas system has rapidly expanded its application range to include diagnostics, therapeutics, and, more recently, live cell imaging. In contrast to traditional fluorescent in situ hybridization, CRISPR/Cas-based imaging systems enable real-time dynamic tracking of genomic sequences down to the level of single cells and even a single locus. Recognizing the vital role played by CRISPR/Cas-based imaging systems in advancing our understanding of genome function in relation to its spatiotemporal organization, this review aimed to depict the current landscape of CRISPR/Cas-based technologies in genomic imaging. It discusses the principles, notable features, advantages, and limitations of these CRISPR/Cas-based imaging systems and concludes with a brief outlook into the future.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

Hepatocellular carcinoma (HCC) cases with small nodules are commonly treated with radiofrequency ablation (RFA), but the recurrence rate remains high. This study aimed to establish a blood signature for identifying HCC with metastatic traits pre-RFA.

Data from HCC patients treated between 2010 and 2017 were retrospectively collected. A blood signature for metastatic HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin, cell-free DNA (cfDNA) mutations, and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA performance. The HCC blood signature was validated in patients prospectively enrolled in 2021.

Of 251 HCC patients in the retrospective study, 33.9% experienced recurrence within 1 year post-RFA. The HCC blood signature identified from these patients included des-γ-carboxy-prothrombin ≥40 mAU/mL with cfDNA mutation score, where cfDNA mutations occurred in the genes of TP53, CTNNB1, and TERT promoter. This signature effectively predicted 1-year post-RFA recurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset, and with 87% specificity and 76% sensitivity in the prospective dataset (n=32 patients). Among 14 cases in the prospective study with biopsy tissues available, positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and microvasculature.

This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease’s early recurrence post-RFA.

Familial hypercholesterolemia (FH) is characterized by an elevated level (>155 mg/dL) of LDL (low-density lipoprotein)-Cholesterol in the blood circulation and is one of the major causes of premature atherosclerotic cardiovascular diseases. The significant genes responsible for this lipid deposition are LDL-Receptor (LDLR), Apolipoprotein B-100 (APOB), and proprotein convertase subtilisin/kexin type 9 genes (PCSK9). Other than these 3 genes, 64 gene loci have been identified as polygenic causes. The aim of the study was to analyze the other genes involved in this condition.

In this study, three datasets representing the markers of monocyte, T lymphocyte, and induced pluripotent stem cells (iPSCs) in atherosclerosis and FH were selected from the pool of hypercholesterolemia datasets, and differential expression analysis was done using networkanalyst.ca.

The monocyte and t-lymphocytes datasets each had 743 differentially expressed genes (DEGs), while the iPSCs dataset contained 691 DEGs. RPS7, AKRIC3, PL9, and OSM were among the genes that were expressed in the majority of Gene ontology annotations.

According to the findings, genes with varied levels of expression are associated with a variety of functions, including membrane transport, ubiquitin-protein ligase activity, the COP9 signalosome complex, the mitochondrial respiratory chain, and copper metabolism. Analyzing these critical genes lays the groundwork for investigating potential therapeutic targets that could alleviate the impact of cardiovascular disease in individuals diagnosed with FH.

Essential oils, known for their pleasant aromas, not only calm the mind and elevate the mood but also captivate the interest of researchers aiming to unveil their vast potential. Various methodologies are employed to explore the diverse capabilities of essential oils, often yielding promising and significant outcomes. This review aims to elucidate the molecular mechanisms of essential oils at the cellular level. It identifies multiple mechanisms through which essential oils exhibit their therapeutic effects across various systems. However, a comprehensive understanding of their fundamental mechanisms still necessitates extensive research. In this review, we discuss the mechanisms underlying the biological activities of essential oils, specifically their antioxidant, antimicrobial, anticarcinogenic, anti-diabetic, and anti-inflammatory properties.

This review highlighted the significant changes in the 2022 WHO classification of kidney epithelial tumors and the rationale behind these revisions. The updates included modifications to the classification of renal epithelial tumors, a greater emphasis on histopathological criteria, a structural reorganization of renal tumor categories, changes to established renal tumors, the creation of a new category for molecularly defined renal tumors, the introduction of an “other renal tumors” category, and the identification of novel, emerging, or provisional tumors and categories. These advancements reflect substantial progress in the diagnosis, classification, and prognostication of genitourinary system tumors, driven by key contributions from molecular studies and immunohistochemistry markers.

Recent therapeutic advances for gastrointestinal tract tumors have focused on targeted therapies and molecular profiling. Anti-human epidermal growth factor receptor (HER) 2 drugs, claudin 18.2 inhibitors, and immune checkpoint inhibitors have shown efficacy in small subgroups of gastric, esophageal, and colorectal cancers, respectively. However, their benefits remain limited, and small bowel carcinomas continue to lack effective treatments. Conventional chemoradiation remains the primary approach for most cases. The future development of therapies for these cancers will depend on understanding the molecular basis of the diseases. This review aims to summarize the main breakthroughs in the knowledge of the molecular basis of gastrointestinal cancers, focusing on those that could lead to significant changes in the management and prognosis of these prevalent and still lethal neoplasms.

Colorectal cancer (CRC) is one of the most frequent causes of cancer-related death worldwide. Chemotherapeutic agents used in CRC treatment include oxaliplatin, irinotecan, leucovorin, Tegafur-Uracil, capecitabine, 5-fluorouracil, and monoclonal antibodies. The development of other effective drugs is urgently needed for CRC patients. As the epigenetics of CRC is increasingly understood, epigenetic modifiers (or epidrugs) targeting epigenetic mechanisms could play an important role in this process. During the past two decades, many studies have demonstrated that many specific genes are silenced by hypermethylation of their promoters in CRC, which means that the expression of these genes could be restored since epigenetic alterations are reversible. In fact, some molecules have been studied for their ability to inhibit DNA methyltransferases, and the results showed that silenced genes were reactivated. These molecules could be natural, such as curcumin, tea polyphenols, quercetin, and nanaomycycin A, or synthetic, such as 5-azacytidine, decitabine, procainamide, and zebularine. On the other hand, we hypothesized in this article that ten-eleven translocation inhibitors could be another class of epigenetic modifiers since they could prevent chromosomal instability through decreasing the global hypomethylation of genomic DNA. Some studies have reported that some ten-eleven translocation inhibitors exhibit anticancer effects, which supports our hypothesis. Additionally, we have proposed combinations of these epigenetic modifiers according to different parameters.

Disseminated carcinomatosis of bone marrow (DCBM) occurs mostly in stomach cancer patients; however, characterizing tumor cells morphologically and phenotypically in the bone marrow is not an easy task. In addition, among patients with DCBM, an unknown primary site (CUPS) is rarely noted despite standard clinical evaluation, imaging studies, and endoscopic findings. This study aimed to clarify the diagnosis/outcome of DCBM in elderly patients we have treated.

Here, we report eight DCBM cases. Once tumor clumps were noted in the bone marrow, we performed serum tumor markers, immunostaining of tumor cells in the bone marrow clot, or biopsy preparations. In addition, imaging studies (CT/MRI/ FDG PET-CT) were performed.

Of eight cases, two were diagnosed with DCBM/CUPS. Among the eight cases, six fatal cases had a median survival time of 2 months (ranging from <0.5 to 8 months) from DCBM detection to death or the time of this writing, while the CUPS cases were still alive at 2+ and 3+ months, respectively. The outcomes of DCBM and DCBM/CUPS, particularly in elderly patients, were dismal, and comprehensive genomic profiling could not be perform in these cases.

The use of conventional morphological/phenotypical characteristics to improve the prognosis of DCBM patients is limited. Consequently, the application of comprehensive genomic profiling is recommended to enhance diagnostic and therapeutic approaches.

Cholestatic liver disease is a group of diseases in which bile acid accumulates in the liver for various reasons, resulting in abnormal liver biochemical indicators and histological damage. Cholestasis can be divided into intrahepatic cholestasis and extrahepatic cholestasis, which will contribute to liver damage and progress to liver fibrosis and cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis are the two most typical cholestatic liver diseases. Ursodeoxycholic acid is currently the first-line treatment for PBC, while obeticholic acid, budesonide and fibrates have also shown good potential in the treatment of PBC. There are currently no official drugs approved to treat primary sclerosing cholangitis, and the use of ursodeoxycholic acid may have certain clinical benefits. At present, progress has been made in new treatment directions for cholestatic liver disease, including fibroblast growth factor 19, cholestyramine, S-adenosyl-L-methionine, steroid drugs, farnesoid X receptor agonists, and more. Considerable progress has been made in the management of cholestatic liver disease but there are still many opportunities and challenges. In this review, we summarized the recommended guidelines for the management of cholestatic disease and the progress of new drug research and development, in order to provide an important reference for the clinical practice of cholestatic liver disease.

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.