Pyrrolizidine alkaloids (PAs), widely distributed in plants, are known to induce liver failure. Hepatic platelet accumulation has been reported during the progression of PA-induced liver injury (PA-ILI). This study aimed to investigate the mechanisms underlying platelet accumulation in PA-ILI.

Cases of PA-ILI, non-PA-ILI, and control subjects were collected from patients hospitalized at Zhongshan Hospital, Fudan University (Shanghai, China) between 2012 and 2019. A mouse model of PA-ILI was established using monocrotaline administration. Liver RNA sequencing was performed, and gene interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database. Low-molecular-weight heparin and recombinant a disintegrin and metalloproteinase with a thrombospondin type I motif member 13 (ADAMTS13) were applied. The necrotic liver area, hepatic platelet accumulation, and von Willebrand factor (VWF) deposition were examined using hematoxylin and eosin staining and immunofluorescence assay.

Hepatic platelet accumulation, necrotic area expansion, and increased VWF expression were observed in both PA-ILI patients and mice. The Search Tool for the Retrieval of Interacting Genes/Proteins database indicated that ADAMTS13 regulates VWF expression and was differentially expressed in the livers of PA-ILI mice. Plasma and hepatic ADAMTS13 levels were significantly downregulated in both PA-ILI patients and mice. Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis.

Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Multiple treatment modalities are available for the management of HCC, depending on its stage as determined by the Barcelona Clinic Liver Cancer staging system. Because liver transplantation (LT) theoretically removes the cancer and replaces the organ at risk for future malignancy, LT is often considered the most definitive and one of the most efficacious treatment options for HCC. Nevertheless, the success and efficacy of liver transplantation depend on various tumor characteristics. As a result, multiple criteria have been developed to assess the appropriateness of a case of HCC for LT, with the pioneering Milan Criteria established in 1996. Over the past 20 to 30 years, these criteria have been critically evaluated, expanded, and often liberalized to make LT for patients with HCC a more universally applicable option. Furthermore, the development of other treatment modalities has enabled downstaging and bridging strategies for HCC prior to LT. In this narrative and comprehensive review, we provided an update on recent trends in the epidemiology of HCC, selection criteria for LT, implementation of LT across different regions, treatment modalities available as bridges, downstaging strategies, alternatives to LT, and, finally, post-LT surveillance.

Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects of N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide (TGN-020), a selective AQP4 inhibitor, on glymphatic function and to assess its impact on short-term behavior in mice.

In this laboratory study, mice were randomly assigned to TGN-020-treated and control groups. We evaluated glymphatic function by measuring the distribution of Evans blue dye in the brain following injection into the cisterna magna. Behavioral assessment of cognitive function was performed using open field and Morris water maze tests. AQP4 protein expression levels were analyzed via immunohistochemistry. Statistical comparisons were conducted using the one-way analysis of variance to evaluate the results among groups.

Our findings revealed that the areas of Evans blue dye in the dorsal (p < 0.001) and ventral (p < 0.001) surfaces of the brain were significantly reduced in the TGN-020 group compared to the control group, indicating impaired glymphatic function. However, behavioral tests demonstrated no significant short-term changes; the mean distance traveled in the open field was 4,345 cm in the control group and 4,049 cm in the TGN-020 group (p = 0.5625), while the mean speed was 2.649 cm/s for controls and 2.868 cm/s for the TGN-020 group (p = 0.6762). In the Morris water maze, latency was comparable (36.33 s for TGN-020 vs. 34.89 s for controls, p = 0.758). Additionally, no significant differences in AQP4 expression intensity were observed between the two groups.

Our study demonstrates that acute inhibition of AQP4 through a single dose of TGN-020 significantly impairs glymphatic function without inducing short-term behavioral abnormalities in mice. These findings contribute to understanding AQP4’s role in the glymphatic system and its potential implications for neurological function.

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.

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.

Prostate cancer is virtually the most common type of cancer, leading to multiple complications within the male gender worldwide. However, prostatic complications have been increasing recently due to probable changes in lifestyles. Affected patients try every treatment technique to confront their cancer. Thus, radiation therapy has been demonstrated to be one of the most efficient lanes of long-term survivorship in men with malignant prostatic cancer. Although radiotherapy has the potential to seem irritating, due to the studies, metastasis-free survival, biochemical recurrence-free survival, and prostate cancer-specific survival have experienced a major increase in various cases of the disease. Subsequently, still, radiation therapy has revealed the superlative approach to avoiding the risk of cancer relapse and case mortalities. This manuscript would radically discuss novel approaches that could probably increase the lifespan and survivorship of patients owning to previous examinations.

The years 2019–2021 of the twenty-first century are synonymous with the COVID era, as the Coronavirus disease 2019 (COVID-19) wreaked havoc and continues to be aggressively persecuted. Globally, about 300 million COVID-19 cases and nearly 5.3 million fatalities have been recorded so far. Since then, the coronavirus RNA genome has rapidly mutated, giving rise to several mutant and recombinant variants. On March 9, 2022, a new recombinant known as Deltacron/Delmicron emerged due to inter-lineage recombination between Delta and Omicron. Many researchers consider it a “grey rhino” occurrence rather than a “black swan” event. However, some groups of scientists claim it is a “laboratory error”. Another COVID-19 variant, XE (a recombination of BA.1 and BA.2), has been discovered, which has a transmission rate ten times higher than the fastest-spreading Omicron subvariant BA.2. Delta and Omicron, two of the most novel strains, co-circulated for many weeks in several parts of the globe, allowing for coinfections and eventual recombination. Consequently, the recombinant strains XD and XF are associated with a very high transmission rate and reduced neutralizing antibody response. Under these circumstances, researchers are rushing to develop a vaccine with high efficacy against the circulating mutants and the variants likely to emerge in the near future. This review article provides recent updates on newly identified sub-variants of Omicron with an in-depth focus on their genomic alterations, infectivity patterns, and pathogenic manifestations.

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.

Albumin is a major prognostic factor for patients with advanced liver disease, dependent on its concentration and biological activity. This study aimed to improve the method of active albumin detection and elucidate its predictive validity of albumin activity across hepatic disease progression and etiology.

This study synthesized a novel ratiometric fluorescent probe with an improved structure of 2′-FBPBN. The technique was used to detect native human albumin (HA) activity in 244 patients with hepatitis B cirrhosis (LC) and 66 patients with hepatocellular carcinoma (HCC). Clinical and laboratory data were also collected.

Patients with LC and HCC were divided into normal albumin and low albumin (LA) groups. The median levels of albumin and HA activity in LC patients were 41.44 g/L and 51.85%, 28.51 g/L and 53.89%, respectively, while in HCC patients, they were 43.19 g/L and 33.69%, 30.77 g/L and 43.63%, respectively. The levels of total bilirubin, prothrombin time, international normalized ratio, native HA activity, Child-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-Na score were significantly higher in the LA groups, while the levels of platelet, cholesterol, and cholinesterase were lower compared to the normal albumin group (P < 0.05). The LA groups were more likely to suffer from hepatic encephalopathy and ascites. Patients with normal active HA had significantly higher survival rates than those with low active HA.

Native HA activity may outperform albumin as a prognostic indicator for assessing the severity of liver disease.