Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Electro-acupuncture treatment ameliorates intestinal inflammatory injury in cerebral ischemia-reperfusion rats via regulating the balance of Treg / γδ T cells.

Electro-acupuncture (EA) has an anti-inflammatory role in ischemic stroke, but whether the protective effect of EA involves the regulation of the intestine barrier and Treg/ γδ T cells is unclear. Cerebral ischemia-reperfusion (I/R) injury was induced by middle cerebral artery occlusion(MCAO) for 2 h followed by reperfusion for 24 h. The rats have treated with EA at the "Baihui" acupoint(GV20). Triphenyl tetrazolium chloride (TTC) staining and Longa neurologic score were performed to evaluate the outcomes after ischemic stroke. Inflammatory factor expression levels in the serum, ischemic hemisphere brain, and small intestine were detected by ELISA or RT-qPCR. Additionally, the morphology change of the small intestine was evaluated by analyzing villus height and smooth muscle thickness. Meanwhile, the expression of tight-junction proteins, including Zonula Occludens-1 (ZO-1), Occludin, and Claudin-1, were detected to evaluate the impact of EA on mucosal permeability in the small intestine. The percentages of regulatory T cells (Tregs) (CD45+CD4+Foxp3+) and γδ T cells (CD45+CD4-γδ T+) were measured to assess the effect of EA on intestinal T cells. EA decreased the brain infarction volume and intestine barrier injury in ischemic stroke rats. At the same time, it effectively suppressed the post-stroke inflammation in the brain and small intestine. More importantly, EA treatment increased the percentage of Tregs in the small intestine while reducing the rate of γδ T cells, and ultimately increased the ratio of Treg/ γδ T cells. These results demonstrated that EA ameliorated intestinal inflammation damage by regulating the Treg/ γδ T cell polarity shift and improving the intestine barrier integrity in rats with I/R injury. This may be one of the mechanisms underlying the anti-ischemic injury effects of acupuncture on stroke.

IDH2: A novel biomarker for environmental exposure in blood circulatory system disorders.

As the risk of harmful environmental exposure is increasing, it is important to find suitable targets for the diagnosis and treatment of the diseases caused. Isocitrate dehydrogenase 2 (IDH2) is an enzyme located in the mitochondria; it plays an important role in numerous cell processes, including maintaining redox homeostasis, participating in the tricarboxylic acid cycle and indirectly taking part in the transmission of the oxidative respiratory chain. IDH2 mutations promote progression in acute myeloid leukemia, glioma and other diseases. The present review mainly summarizes the role and mechanism of IDH2 with regard to the biological effects, such as the mitophagy and apoptosis of animal or human cells, caused by environmental pollution such as radiation, heavy metals and other environmental exposure factors. The possible mechanisms of these biological effects are described in terms of IDH2 expression, reduced nicotine adenine dinucleotide phosphate content and reactive oxygen species level, among other variables. The impact of environmental pollution on human health is increasingly attracting attention. IDH2 may therefore become useful as a potential diagnostic and therapeutic target for environmental exposure-induced diseases.

[Health Risk Assessment and Environmental Benchmark of Heavy Metals in Cultivated Land in Mountainous Area of Northwest Guizhou Province].

An extensive investigation of heavy metal (Cd, Hg, As, Pb, and Cr) levels in 137 pairs of soil-maize/rice samples was conducted in cultivated land from a typical karst mountain area in the Northwest of Guizhou Province. A health risk assessment model was used to assess the health risks of those areas, and the environmental benchmarks of heavy metals in soils were evaluated using the species sensitivity distribution (SSD) model. The results showed that the soils of maize and rice were polluted by heavy metals. Cd was the primary pollutant, with an exceeding rate ranging from 87% to 445%. The contaminated level of maize fields was higher than those of rice fields. In contrast, only 3.51% and 13.4% of Cd content in maize kernels and rice grains exceeded the national threshold, and the Cd heavy metal accumulation ability of rice was higher than that of maize. The carcinogenic and non-carcinogenic risks of heavy metals for adults and children in the study area were at a low level. The carcinogenic risk of rice consumption was slightly higher than that of maize, and the health risk to children was higher than that to adults. The results derived from the SSD method showed that the 95% and 5% hazardous concentrations (HC5 and HC95) of maize fields were 0.67 for Cd, 771.99 for As, 40.85 for Pb and 609.88 for Cr mg·kg-1, and HC95were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of rice fields were 2.42 for Cd, 8.88 for As, 41.41 for Pb and 27.84 for Cr mg·kg-1, and the HC95 values were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of Cd, As, and Cr in maize fields and Cd in rice fields were significantly higher than the soil risk screening values in the current standard, and the HC95 values of the two fields were higher than the soil risk intervened values. The results indicated that the current standard would be too strict to evaluate the actual pollution level of soil heavy metals in this area.

[Research Progress of FAM60A in the Regulation of Cellular Function].

FAM60A,a cell cycle protein,is a subunit of the SIN3 transcription regulator family member A/histone deacetylase(SIN3-HDAC)complex and plays an important role in cell cycle regulation,cell morphology change,cell proliferation,differentiation and migration,early embryogenesis and so on.Studies in recent years have shown that FAM60A plays a role in the occurrence and development of tumors including human osteosarcoma,esophageal cancer,gastric cancer,lung cancer and liver cancer,providing a new research direction for tumor diagnosis and treatment.Based on the research results in recent years at home and abroad,this paper discussed the effects of FAM60A on cellular functions.

Multiple schwannomas with pseudoglandular element synchronously occurring under the tongue: A case report.

BACKGROUND: Schwannoma is a rare benign, encapsulated tumor of the nerve sheath under the tongue, mostly occurring as solitary tumors with classical histological pattern and several common morphological variants. To our knowledge, multiple schwannomas with pseudoglandular element synchronously occurring under the tongue are rare; we report herein the first such case. CASE SUMMARY: A 53-year-old man had first noticed an isolated asymptomatic mass under the tongue, and as the mass grew, the tongue was elevated. Physical examination showed multiple oval neoplasms, and the overlying mucosa was normal. Computed tomography showed three low-density oval neoplasms under the tongue, which were cystic-solid with unclear boundary. The patient has no cutaneous tumors, VIII nerve tumors, or lens opacities and no history of neurofibromatosis 2 or confirmed schwannomatosis in any first-degree relative. Magnetic resonance imaging showed no evidence of vestibular schwannoma. The preoperative diagnosis was mucoepidermoid carcinoma. During hospitalization, all neoplasms were completely excised by surgeons through an intraoral approach under general anesthesia. The diagnosis of the multiple schwannomas with pseudoglandular element was made by histopathology after surgery. At the 15-mo follow-up visit, the patient had no sign of recurrence or development of other peripheral nerve tumors. CONCLUSION: Although rare, multiple schwannomas with pseudoglandular element do exist in patients presenting with masses under the tongue. Oral surgeons should be aware of the existence of multiple schwannomas with pseudoglandular element when considering masses under the tongue due to the different prognosis between multiple schwannomas with pseudoglandular element and mucoepidermoid carcinoma.

[Toxicology and bioactivities of CO-releasing molecules based on cobalt complexes].

Complexes containing cobalt and carbon monoxide ligands, CO releasing molecules(CORMs), have the potential of anti-tumor and anti-inflammatory. In this paper, three hybrid CORMs 1-3 were synthesized and tested for their toxicology in vivo and bioactivities. The results suggest that the complexes have a long half-life in the range of 43-53 min; their oral LD(50) to mouse are between 1 500 mg·kg(-1) and 5 000 mg·kg(-1). After the successive administration, complex 1 exhibited a toxic activity in rats' liver, and induced an injury to liver cells. Complex 1 had a strong growth inhibition activity(IC(50) 36.20 µmol·L(-1) and 39.25 µmol·L(-1)) in both He La cells and Hep G2 cells, complex 2 displayed a lower activity in the inhibition of He La cells proliferation than the control 5-FU(IC(50) 114.19 µmol·L(-1)), but had a higher activity in the inhibition of Hep G2 cells than the control 5-FU(IC(50) 171.34 µmol·L(-1)). The anti-inflammatory study suggests that all of them reduce intracellular nitrite level, complexes 1 and 2 have a stronger activity than complex 3. Their anti-inflammatory activity attributes to the CO molecules of the CORMs, which was confirmed by comparison with the corresponding ligand.

[Toxicology and tissue distribution of Ruthenium (II) CO-releasing molecules and its interaction with endogenous substances].

Carbon monoxide has been proved to be an important signal molecule in body. Transition metal carbonyl compounds are solidified form of carbon monoxide. Numerous studies have shown that Ruthenium carbonyl carbon monoxide releasing molecules have a strong pharmacological activity. In this paper, five Ruthenium (II) carbonyl CORMs 1-5 were synthesized and their toxicology, tissue distribution and interaction with blood endogenous substances were investigated. The results showed CORMs' IC50 to fibroblasts are ranged from 212.9 to 2089.2 micromol x L(-1). Their oral LD50 to mouse is between 800 to 1600 mg x kg(-1). After repeated administration, CORMs 1 and CORMs 5 haven't shown an obvious influence to rats' liver and kidney function, but caused the injury to liver and kidney cells. The in vivo distribution result revealed the majority of CORMs were distributed in blood, liver and kidney, only a small part of CORMs distributed in lung, heart and spleen. They could scarcely cross the blood-brain barrier and distribute to brain. The non-CO ligands in structure have an obvious relevance to their in vivo absorption and distribution. Interestingly, CORMs could enhance the fluorescence of bovine serum albumin, and this enhancement was in direct proportion with the concentration of CORMs. Under different conditions, interaction of CORMs with glutathione got different type of products, one is Ruthenium (II) tricarbonyl complexes, and Ruthenium (II) dicarbonyl complexes.

Correlation of COX-2 and K-ras expression to clinical outcome in gastric cancer.

Recent studies have suggested that K-ras play an important role in the induction of COX-2 expression in tumor cells. In the present study, tumor samples of 89 gastric cancer patients were prepared in tissue microarrays and they were stained by immunohistochemistry with antibodies against COX-2 and K-ras. We investigated the relationship between the protein expressions of COX-2 and K-ras in gastric cancer and their significance as prognostic markers in gastric cancer patients. The over expression rate of COX-2 and K-ras in gastric cancer was 61.8% and 61.8% (55/89) of all the patients, respectively. There was a significant positive correlation between COX-2 and K-ras expression in gastric cancer. COX-2 and K-ras positivity were correlated with depth of invasion and lymph node metastasis, respectively. K-ras positivity was correlated with growth pattern. Patients with COX-2 and K-ras positive tumors had a poorer prognosis than those with COX-2 and K-ras negative tumors. Over expression of COX-2 and K-ras were closely correlated to prognostic of patients with gastric cancer and they educed synergistic effect with carcinogenesis and development in gastric cancer.