End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.

This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.

Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.

Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.

Cholesterol synthesis and gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is a metabolite of gut microbiota. However, the underlying mechanisms of TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore the specific molecular mechanisms through which TMAO promotes gallstone formation.

Enzyme-linked immunosorbent assays were used to compare serum concentrations of TMAO, apolipoprotein A4 (APOA4), and proprotein convertase subtilisin/kexin type 9 (PCSK9) between patients with cholelithiasis and normal controls. A murine model of TMAO-induced cholelithiasis was employed, incorporating assays of gallstone weight and bile cholesterol content, along with RNA sequencing of murine hepatic tissue. A TMAO-induced AML12 hepatocyte line was constructed and transfected with targeted small interfering RNAs and overexpression plasmids. In vivo and in vitro experiments were performed to determine the expression and regulation of genes related to cholesterol metabolism.

Serum TMAO and PCSK9 levels were elevated, whereas APOA4 levels were reduced in patients with cholelithiasis. Furthermore, our murine model demonstrated that TMAO upregulated hepatic expression of PCSK9, 3-hydroxy-3-methylglutaryl-CoA reductase, and ATP-binding cassette sub-family G member 5/8, while reducing APOA4 expression, thereby modulating cholesterol metabolism and promoting lithogenesis. PCSK9 and APOA4 were identified as key regulatory genes in the cholesterol metabolic pathway. PCSK9 knockdown increased APOA4 expression, while APOA4 overexpression led to reduced PCSK9 expression.

TMAO upregulated hepatic PCSK9 expression and reduced APOA4 expression, initiating a feedback loop that dysregulated cholesterol metabolism and promoted lithogenesis.

Mesothelioma is an aggressive tumor with a poor prognosis. Histological diagnosis of mesothelioma using limited tissue samples can be challenging. Carbonic anhydrase IX (CAIX) is a transmembrane protein that is overexpressed in a variety of solid tumors. This study aimed to investigate the clinical utility of CAIX expression in the differential diagnosis of pleural mesothelioma from non-small cell lung carcinoma (NSCLC).

Unstained tissue microarray slides composed of 56 cases of pleural mesothelioma and 82 cases of NSCLC were subjected to immunohistochemical staining using a mouse anti-human antibody against CAIX.

Of the 38 epithelioid mesothelioma cases, 34 (89%) displayed diffuse and strong cytoplasmic membrane reactivity, while the remaining four cases (11%) showed weak to moderate staining in tumor cells. Five out of sixteen (5/16) sarcomatoid mesothelioma cases were negative. Among the non-small cell lung carcinoma cases, 76% (32/42) of adenocarcinomas and 57% (21/37) of squamous cell carcinomas were completely negative, whereas the remaining cases showed focal weak expression of CAIX.

Our study demonstrates that CAIX expression has a high sensitivity (100%) in detecting pleural epithelioid mesothelioma, which is comparable to or better than currently used mesothelial markers. The specificity of CAIX is within a comparable range to that of commonly used mesothelial markers for differentiating epithelioid mesothelioma from NSCLC. Therefore, we recommend that CAIX immunohistochemistry staining be considered as an additional tool for the differential diagnosis of mesothelioma, particularly pleural epithelioid mesothelioma, from its common mimicker, NSCLC.

The spatial heterogeneity of tumors has long been a subject of significant interest in oncology. Recent research has revealed that tumors and their microenvironments undergo dynamic changes over time, particularly in the form of periodic circadian rhythms. Disruptions to these rhythms have been recognized as a pivotal factor in the advancement of tumorigenesis. Such disruptions not only induce dysregulation of gene expression within tumor cells, influencing tumor growth, metabolism, the cell cycle, and vascular homeostasis but also facilitate metastasis. Furthermore, they mediate the remodeling of the tumor immune microenvironment, fostering the development of an immunosuppressive milieu. Additionally, the in vivo metabolism and therapeutic responsiveness of tumor treatments—including chemotherapy, targeted therapy, and immunotherapy—have been shown to be modulated by circadian rhythms. This suggests that time-specific drug administration may enhance treatment efficacy, offering novel insights for precision cancer therapy. In this review, we systematically update contemporary research on the impact of circadian rhythms on tumor biology, encompassing both tumor progression and the efficacy of drug therapies. Building upon these insights, we explore the potential for a synergistic approach that integrates the targeting of rhythmic genes with current tumor treatment modalities. We also discuss the feasibility of tailoring tumor therapy to the rhythmic alterations that define in vivo metabolism and the efficacy of specific therapeutic agents, highlighting the significance of rhythm-based strategies in the personalized treatment of tumors and the prevention of associated diseases.

Gelsemium elegans Benth (G. elegans) is a traditional medicinal plant; however, it is highly toxic, and toxicity varies significantly between species. The cause of this difference has not been clarified. Humantenirine is an important toxic alkaloid in G. elegans, and its metabolism has been poorly studied. This study aimed to compare the different metabolites formed by human liver microsomes, pig liver microsomes, and goat liver microsomes.

High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used to study the metabolism of humantenirine in human liver microsomes, pig liver microsomes, and goat liver microsomes.

A total of eight metabolites (M1-M8) were identified, and three major metabolic pathways were found: demethylation (M1), dehydrogenation (M2, M3, M7), and oxidation (M4, M5, M6, M8).

Based on these results, it is hypothesized that demethylation is the major detoxification pathway for humantenirine, providing important information to better understand the metabolism and toxicity differences between species of G. elegans.

Type 1 bipolar disorder (BP) is a mental illness characterized by extreme shifts in mood, oscillating between manic and depressive episodes. It ranks as the sixth most prevalent psychiatric disorder globally, often emerging in the teenage years. This study aimed to identify associations between BP and 15 insertion/deletion (Indel) polymorphisms in the human genome, examining genes including TPA, UCP2, HLA-G, FADS2, ADRA2B, VEGF, PDCD6IP, SLC6A4, TLR2, APOB, TP53, LRPAP1, DHFR, MDM2, and DBH.

This case-control study involved 226 patients with BP and 235 healthy controls. Allele frequencies for each polymorphism in cases and controls were estimated using pooled samples. Polymerase chain reaction was performed for each Indel polymorphism using pooled samples as templates to estimate allele frequencies.

The data presented herein demonstrate a significant association between a 14bp Ins/Del polymorphism in the HLA-G gene and the risk of BP. The deletion allele of this polymorphism increased the risk of BP (odds ratio = 1.434, 95% confidence interval = 1.106–1.859, p = 0.007). Other 14 Indel polymorphisms were not associated with the risk of BP.

The HLA-G 14bp Indel polymorphism exhibits a significant correlation with the risk of BP in this study. This finding contributes to understanding the etiology of BP.

Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.

Ten ALS patients were randomly assigned to either a treatment group (electroacupuncture with Chinese herbal medicine, n = 6) or a control group (waiting treatment, n = 4). Healthy controls (age- and sex-matched, n = 10) were also included. Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months. ALS functional rating scale scores were documented pre- and post-treatment. Stool samples were collected at two time points (T0 and T4 weeks) and analyzed, and metabolomic profiles from urine samples were analyzed post-treatment. Heatmap correlation analysis was used to explore relationships between microbiota, metabolomics, and clinical outcomes.

Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group. A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores (P < 0.005 and P < 0.001, respectively). Differential expression of purine metabolism was observed in ALS patients (P = 0.0017).

Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS. These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine. Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.

Molecular analysis of breast cancer tissue has revealed that breast cancer is not a uniform disease. Each breast cancer patient has several molecular signatures that differ from those of others. Therefore, breast cancer therapy should be personalized, depending on its molecular signatures. Breast cancer with hormonal receptors can be treated with a selective estrogen receptor modulator or selective estrogen receptor degrader therapy, while breast cancer with overexpression of human epidermal growth factor receptor 2 (HER2)-neu gene responds excellently to anti-HER2-neu therapy. For patients with advanced breast cancer that already has distant metastasis and a poor prognosis, a new agent has been discovered. The phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibitor has been proven effective in treating advanced breast cancer with a PIK3CA gene mutation. This therapy can be administered to HER2-negative breast cancer patients and in combination with selective estrogen receptor degrader therapy for post-menopausal patients with positive hormonal receptors. Although this treatment is effective, it cannot be given to every advanced breast cancer patient. Before administering the treatment, a PIK3CA mutation test is compulsory. PIK3CA mutation detection in breast cancer can predict the cancer’s response to the PIK3CA inhibitor, providing information on which patients will benefit from the treatment.

The Chinese caterpillar fungus Ophiocordyceps sinensis (Berk.) is a valuable traditional medicine, also known throughout Asia by its Tibetan name དབྱར་རྩྭ་དགུན་འབུ (Yartsa Gunbu), meaning “summer grass, winter worm”. The mature fungus O. sinensis contains abundant active biological components, including polysaccharides, alkaloids, amino acids, inorganic elements, and others. Studies have previously confirmed that O. sinensis possesses multiple pharmacological activities. Therefore, it holds high value in the commercial market and is in increasing demand. However, the unique formation process and harsh growth environment contribute to the preciousness and scarcity of the species. To meet market demand, multiple mycelium types have been isolated from natural O. sinensis and cultivated artificially using fermentation technology. Currently, both natural and cultivated O. sinensis products are available as healthy Chinese herbal medicines on the market. However, there is a lack of comparative reviews on the two types of O. sinensis in terms of their compositions and medicinal functions. This mini-review will focus on the bioactive ingredients and medicinal functions of both natural and cultivated O. sinensis, intending to elucidate their medical values as traditional Chinese medicines for human use.

Nail psoriasis is common in patients with plaque psoriasis and is associated with morbidity, including onychomycosis, which can complicate psoriasis treatments and be difficult to differentiate. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is a fast and simple technique for identifying microorganisms through protein analysis. This study aimed to determine the sensitivity and specificity of MALDI-TOF for diagnosing onychomycosis in patients with nail psoriasis, by using conventional mycological and histological methods as the reference standard.

A prospective study was conducted on 88 patients with clinically and histopathologically confirmed nail psoriasis. One hundred nail samples were obtained for direct examination, fungal culture, and mass spectrometry. None of the patients were receiving antifungal or systemic immunosuppressive therapy at the time of sampling.

Potassium hydroxide preparation and fungal culture were positive in 58 out of 100 nail samples from patients with psoriasis. MALDI-TOF identified onychomycosis in 68 out of 100 samples, distinguishing these cases from nail psoriasis without onychomycosis (32 out of 100). An excellent correlation (0.95) was found between MALDI-TOF and conventional onychomycosis diagnostic methods. The sensitivity and specificity of MALDI-TOF for diagnosing onychomycosis in patients with psoriatic nails were 95.4% and 97.5%, respectively.

MALDI-TOF can be used to accurately differentiate cases of nail psoriasis without infection from those with onychomycosis.