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Background: The volumetry of the hippocampal subregion may provide additional information in the early investigation of amnestic mild cognitive impairment (aMCI) and the T2 signal intensity (T2-SI) of the hippocampal subregion has not been well studied quantitatively by magnetic resonance imaging (MRI) in aMCI. Methods: Using combined MRI-based hippocampal volumetry and T2-SI at the levels of the whole hippocampus and hippocampal subregion, 18 patients with aMCI and 18 age-matched controls were investigated. Results: Significantly lower left whole hippocampal and hippocampal head volumes and higher T2-SI in the bilateral whole hippocampus and hippocampal head were shown, whereas atrophy of the right whole hippocampus and hippocampal subregion was not significant in aMCI. Additionally, correlations were found among the hippocampal volume, T2-SI and Mini-Mental State Examination (MMSE) scores for aMCI in the whole hippocampus and some hippocampal subregions and an almost perfect correlation was found between T2-SI of the left hippocampal head and MMSE scores regarding aMCI (r = –0.831, P = 0.000). Conclusion: Abnormalities of the hippocampal volume and T2-SI were documented in aMCI, whereas T2-SI was implied to be more susceptible than the volume in the pathohistological progression in aMCI. Additionally, T2-SI in the left hippocampal head may be a potential biomarker to facilitate the early diagnosis of aMCI. [ABSTRACT FROM AUTHOR]

Small-cell gallbladder neuroendocrine carcinoma (GB-SCNEC) is a relatively rare histological type of gallbladder cancer, and the genomic landscape of GB-SCNEC is rarely considered in treatment decisions. We performed whole-genome sequencing on an advanced case of GB-SCNEC. We identified approximately 900 high-quality somatic single nucleotide variants (SNVs) and small insertions and deletions (INDELs), 109 of which were shared by both the primary and metastatic tumor tissues. Somatic non-synonymous coding variations with damaging impact in HMCN1 and CDH10 were observed in both the primary and metastatic tissue specimens. A pathway analysis of the genes mapped to the SNVs and INDELs revealed gene enrichment associated with axon guidance, ERBB signaling et al. Furthermore, we identified 11 deletions, 4 tandem duplications and 5 inversions that mapped to known genes. Two gene fusions, NCAM2-SGCZ and BTG3-CCDC40 were also discovered and validated by Sanger sequencing. Additionally, we identified genome-wide copy number variations and microsatellite instability. In this study, we identified novel biological markers of GB-SCNEC that may serve as valuable prognostic factors or indicators of treatment response in patients with GB-SCNEC with lymphatic metastasis. [ABSTRACT FROM AUTHOR]

Background: Fufang Yinhua Jiedu (FFYH) granules are recommended for treating coronavirus pneumonia (COVID-19) in China. However, its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity and clinical efficacy against COVID-19 remain to be confirmed., Aims: Our study aimed to investigate the anti-SARS-CoV-2 effect and potential mechanism of FFYH., Materials and Methods: The activity of FFYH against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated via cell pathogenic effects, immunoblotting, immunofluorescence staining, and qRT-PCR. The potential mechanism of FFYH against SARS-CoV-2 was investigated by immunoblotting. One head-to-head randomized controlled trial was designed to evaluate the clinical efficacy of FFYH in mild COVID-19. Two hundred patients were randomly recruited to receive either FFYH or LHQW (Lianhua Qingwen) granules., Results: The in vitro results indicated that FFYH effectively inhibited SARS-CoV-2 replication by suppressing CPE and decreasing viral RNA and protein expression. A time-of-drug-addition assay confirmed that FFYH mainly targeted the binding and replication stages of the SARS-CoV-2 life cycle. Mechanistic studies revealed that blocking SARS-CoV-2-triggered autophagy may be the primary mechanism by which FFYH protects against SARS-CoV-2 infection by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Clinical results confirmed that FFYH effectively shortened the recovery time of clinical symptoms and viral nucleic acid negativity, improved abnormal hematology parameters, and controlled excessive cytokine responses in mild COVID-19 patients. Subgroup analysis revealed that FFYH improved the recovery time of clinical symptoms, improved hematological parameters, and controlled excessive cytokine storms to a greater extent in the mild COVID-19 male subgroup, abnormal hematology subgroup, and 32-42-year-old subgroup than in the corresponding LHQW subgroup ( P < 0.05). No patients progressed to severe or critical cases., Conclusion: Our results indicate that FFYH not only has good anti-viral activity against SARS-CoV-2 but also has significant efficacy against COVID-19, indicating that FFYH may be a novel complementary option for treating COVID-19., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zheng, Qi, Wei, Mao, Su, Chen, Feng, Qiao, Ma, Tang, Zhou, Zhuang and Zhang.)

Rationale: Male infertility is a common reproductive system disease manifested as aberrant spermatogenesis and identified as "kidney deficiency and dampness" in Chinese traditional medicine. Youjing granule (YG) is a Chinese material medica based on tonifying kidneys and removing dampness. It has proven to be able to regulate semen quality in clinical application, but the underlying mechanism has not been clarified., Methods: Using serum containing YG to treat primarily cultured spermatogonial stem cells (SSCs), the apoptotic rate and mitosis phase ratio of SSCs were measured. The liquid chromatography-tandem mass spectrometry with tandem mass tags method was applied for analyzing the serum of rats treated with YG/distilled water, and proteomic analyses were performed to clarify the mechanisms of YG., Results: Totally, 111 proteins in YG-treated serum samples were differentially expressed compared with control groups, and 43 of them were identified as potential target proteins, which were further annotated based on their enrichment in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Proteomic analyses showed that the mechanisms of YG may involve regulation of glycolysis, gluconeogenesis and nucleotide-binding and oligomerization domain-like receptor signaling pathway. In addition, RhoA and Lamp2 were found to be possible responders of YG through reviewing the literature., Conclusions: The results demonstrate that our serum proteomics platform is clinically useful in understanding the mechanisms of YG., (© 2023 John Wiley & Sons Ltd.)

Multiple functions incorporated in one single-component nanoplatform pave the way for important biomedicine applications. Herein, a multifunctional terbium-doped gadolinium orthophosphate (GdPO 4 :Tb-EDTA) nanoplatform was prepared through a simple, ecofriendly, one-step hydrothermal method. Results showed that dipicolinic acid (DPA), the biomarker of bacterial spores, significantly increased the fluorescence intensity of this nanoplatform and conferred it with rapid response and excellent selectivity. Subsequently, the fluorescence of the ensemble GdPO 4 :Tb-EDTA-DPA can be remarkably quenched by Cu 2+ , which led to a rewritable nanosensor used in the detection of cysteine (Cys) with excellent sensitivity. In addition, GdPO 4 :Tb-EDTA can also be a potential T 1 -weighted magnetic resonance imaging (MRI) contrast agent, which indicated a satisfactory in vitro MRI with r 1 relaxivity values of 13.9 mM -1 s -1 and in vivo MRI through intravenous administration on a rat model. Overall, the proposed assay may have great theoretical and practical significance for designing multifunctional biomaterials.

The aim of the current study was to investigate the effect of the PKM2 gene on the proliferation, invasion, migration and apoptosis of Panc‑1 and Sw1990 pancreatic cancer cells via its interaction with the mitogen‑activated protein kinases (MAPKs) signaling pathways. The expression levels of PKM2 protein in pancreatic cancer cells and the corresponding normal tissues was determined with western blot analysis. Immunohistochemical analysis of PKM2 expression was carried out in paraffin‑embedded sections of pancreatic cancer tissue. Two human pancreatic cancer cell lines were cultured in vitro, and a small interfering RNA (siRNA) was designed for the PKM2 gene and transfected into the cells. Cell proliferation was measured via an MTT assay, cell migration and invasion was measured via Transwell® chambers, and the effect of PKM2 on apoptosis was detected from B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein expression levels. Protein expression levels of the MAPK pathway proteins extracellular signal‑regulated kinase 1/2 (ERK1/2), p38 and c‑Jun N‑terminal kinase (JNK) and their phosphorylated forms were measured via western blot analysis. The expression level of PKM2 was significantly upregulated in the pancreatic cancer tissue compared with that of the corresponding normal tissue. Downregulation of PKM2 expression reduced the proliferation, migration and invasion of pancreatic cancer cell lines, while increasing the levels of apoptosis. Additionally, the expression levels of the phosphorylated‑(p‑)ERK1/2 and p‑p38 of the MAPK pathway in the PKM2 siRNA groups were markedly downregulated compared with those of the controls; however, the expression levels of ERK1/2, p38, JNK, p‑p38 and p‑JNK had no significantly changes compared with those of the control groups. In summary, the PKM2 gene has an important role in the proliferation, invasion, migration and apoptosis of Panc‑1 and Sw1990 pancreatic cancer cells, which may be associated with the expression of ERK1/2 and p38 of the MAPK signaling cascade.

In order to investigate the mechanism of human esophageal Eca109 cells induced by Diosgenin (Dio), the p38 specific inhibitor SB203580 was used to inhibit the expression of p38 and Western blot was employed to detect the effect of SB203580 in Eca109 cells. MTT experiments were executed to detect the proliferation of the cells. Western blot was also applied to find the expression of phosphorylated p38 (p-p38). It is found that SB203580 can inhibit the expression of p38 in human esophageal cell Eca109. After treated with 50 μg/mL of Dio and 10 μg/mL of SB203580, the proliferation of cells showed significantly increase and the apoptosis of cells showed significantly decrease compared with the proliferation in the cells treated with Dio only. Moreover, p-p38 protein level was significantly decreased after treated by the two drugs. It is concluded that Dio may regulate esophageal Eca109 cells through p-p38 pathway.

In order to find the possible mechanism of Dexamethasone (Dex) during curing fibrosis, the bleomycin (BLM)-induced mice model was used. After fibrosis were induced by BLM, histopathological evaluation and RT-PCR were employed to detect the expression of TGF-β1, Smad3 and STAT1. It was found that BLM promoted the development of inflammation, leading to severe pulmonary fibrosis with the increasing of TGF-β1, Smad3 and STAT1. After Dex treatment, the expression of TGF-β1, Smad3 and STAT1 showed a little higher with alleviation of the fibrosis. Thus it is concluded that there is a possible pathway of mouse pulmonary fibrosis model through TGF-β, Smad3 and JAK-STAT pathway.