Comparison of features and outcomes between HIV-negative patients with Cryptococcus gattii meningitis and Cryptococcus neoformans meningitis in South China.

OBJECTIVES: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM). METHODS: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China. RESULTS: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035). CONCLUSIONS: This study demonstrated that species identification helps to guide therapy and predict outcomes.

PEITC triggers multiple forms of cell death by GSH-iron-ROS regulation in K7M2 murine osteosarcoma cells.

Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC50 value of 33.49 µM at 24 h. PEITC (1, 15, 30 µM) dose-dependently inhibited the cell proliferation, caused G2/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher dose of PEITC (90 mg/kg every day) compromised its anti-osteosarcoma effect. Histological examination showed that multiple cell death processes were initiated, iron metabolism was altered and MAPK signaling pathway was activated in the tumor tissues. In conclusion, we demonstrate that PEITC induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. PEITC has promising anti-osteosarcoma activity. This study sheds light on the redox signaling-based chemotherapeutics for cancers.

Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Mining and Validation of Novel Hemp Seed-Derived DPP-IV-Inhibiting Peptides Using a Combination of Multi-omics and Molecular Docking.

Hemp seed-derived inhibitors of dipeptidyl peptidase IV (DPP-IV) demonstrate potential as novel therapeutics for diabetes; however, their proteome and genome remain uncharacterized. We used multi-omics technology to mine peptides capable of inhibiting DPP-IV. First, 1261 and 1184 proteins were identified in fresh and dry hemp seeds, respectively. Simulated protease cleavage of dry seed proteins yielded 185,446 peptides for virtual screening to select the potential DPP-IV-inhibiting peptides. Sixteen novel peptides were selected according to their DPP-IV-binding affinity determined via molecular docking. In vitro DPP-IV inhibition assays identified the peptides LPQNIPPL, YPYY, YPW, LPYPY, WWW, YPY, YPF, and WS with half-maximal inhibitory concentration (IC50) values lower than 0.5 mM, which were 0.08 ± 0.01, 0.18 ± 0.03, 0.18 ± 0.01, 0.20 ± 0.03, 0.22 ± 0.03, 0.29 ± 0.02, 0.42 ± 0.03, and 0.44 ± 0.09 mM, respectively. The dissociation constants (KD) of the 16 peptides ranged from 1.50 × 10-4 to 1.82 × 10-7 M. Furthermore, Caco2 and INS-1 cell assays showed that all 16 peptides could efficiently inhibit DPP-IV activity and increase insulin and glucagon-like peptide-1 concentrations. These results demonstrate a well-established and efficient method to isolate food-derived therapeutic DPP-IV-inhibiting peptides.

Chronic Administration of 13-cis-retinoic Acid Induces Depression-Like Behavior by Altering the Activity of Dentate Granule Cells.

Depression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-cis-RA application increased neural activity in the dentate gyrus (DG) using c-Fos immunostaining, which may be critically involved in some aspects of depression-like behavior. Therefore, we assessed electrophysiological functions by obtaining whole-cell patch-clamp recordings of dentate granule cells (DGCs), which revealed that chronic 13-cis-RA treatment shifted the excitatory-inhibitory balance toward excitation and increased intrinsic excitability. Furthermore, a pharmacogenetic approach was performed to repeatedly silence DGCs, and this manipulation could rescue depression-like behavior in chronically 13-cis-RA-treated mice, suggesting DGCs as a potential cellular target for the direct alleviation of 13-cis-RA-induced depression.

A Novel Cuproptosis-Related Signature Identified DLAT as a Prognostic Biomarker for Hepatocellular Carcinoma Patients.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancers, with more than a million cases per year by 2025. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosis-related genes (CRGs) in HCC remain largely unknown. Methods: In the present study, we constructed and validated a four CRGs signature for predicting the overall survival (OS) of HCC patients in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Results: Patients with high CRGs risk score showed shorter OS than those with low CRGs risk score. Functional analysis suggested that the CRGs-based prognostic signature was associated with metabolism remodeling which facilitated liver cancer progression. In addition, reduced infiltration of CD8+ T cells and increased macrophages were found in HCCs from patients with high CRGs risk score. As one of the four CRGs, higher expression of dihydrolipoamide S-acetyltransferase (DLAT) was accompanied by higher expression of program death ligand 1 (PD-L1) in HCC. Further, we confirmed that DLAT was up-regulated and correlated with poor prognosis in a clinical HCC cohort. Conclusion: In conclusion, our study constructed a four CRGs signature prognostic model and identified DLAT as an independent prognostic factor for HCC, thus providing new clues for understanding the association between cuproptosis and HCC.

Effects of bioactive components of Pu-erh tea on gut microbiomes and health: A review.

Pu-erh tea is a post-fermentation tea with unique flavor and multiple health benefits. Due to the various microorganisms involved in the post-fermentation process, Pu-erh tea contains highly complex components, which have rich interactions with the gut microbiomes (GMs). Because the structure and homeostasis of GMs are closely related to human wellness and the various diseases progress, the beneficial effects of Pu-erh tea on GMs have a great potential for application in health care. However, there is no systematic summary of the bioactive components of Pu-erh tea, and their effects on the GMs. Here, we review the current studies on the effects of Pu-erh tea and its bioactive components on the structure of GMs as well as on health improvement, and further discuss the relevant quality indicators. This "components - function - indicators" clue will hopefully stimulate the standardization of Pu-erh tea fermentation process and the development of its functional products.

[Study on the influence of mineralizer on the structures and spectral properties of calcium aluminates].

The present paper investigated the effect of mineralizer on the structure and properties of calcium aluminates formation. Calcium aluminates powder was synthesized under high temperature calcination by mixing bauxite, limestone and a certain amount of mineralizer. The product structure, compositional information and spectral properties were carefully characterized by XRD, IR and DTA-TG, and the mineralization mechanism of mineralizer was studied during the process of calcium aluminates preparation. The results showed that calcium aluminates powder could be obtained under lower temperature calcination after adding mineralizer to the raw materials. The main products of the reaction were CaAl10 O18 and CaAl2 Si2 O8 without mineralizer, however, the main products of the reaction were CaAl3 BO7 and Ca3 Al10 O18 with mineralizer, in which Al2 O3s could be extracted easily, while CaAl2 Si2 O8 was reduced greatly in which Al2 O3 could not be extracted easily. At the same time, it is easy for calcspar to decompose after adding mineralizer. It is favorable to Al-Si bond break and Al stripping from bauxite. These facts could improve the extraction rate of Al2 O3 from raw materials. Also, in the case of adding mineralizer to the raw mixes, the crystal structure and composition are changed, which is beneficial to reducing calcination temperature.

Association of ultrafine particles with cardiopulmonary health among adult subjects in the urban areas of northern Taiwan.

The association between short-term exposure to particulate air pollution, especially fine particles, and cardiopulmonary health has been well-established in previous studies. However, previous findings regarding the effect of ultrafine particles (UFPs) on cardiopulmonary health are inconsistent. We repeatedly measured the mass concentrations of UFPs using a Micro-Orifice Uniform Deposit Impactor (MOUDI) in the apartments of 100 adult participants and collected the participants' health data from the pulmonary outpatient unit of Shuang-Ho Hospital to investigate the association between short-term exposure to UFPs and cardiopulmonary health using mixed-effects models from January 1, 2014 to August 31, 2017. We also collected ambient air pollution monitoring data from the Taiwan Environmental Protection Administration for data analysis. We observed that an interquartile range increase in the 24-hour mean UFPs (0.97 µg/m3) was associated with a 6.3% [95% confidence interval (CI) = 2.9, 9.7], 5.6% (95% CI = 4.1, 7.1) and 8.5% (95% CI = 3.9, 13.1) increase in systolic blood pressure, diastolic blood pressure and high sensitivity-C-reactive protein, respectively. We also observed the association of particulate matter less than or equal to 2.5 µm in diameter and nitrogen dioxide with increased blood pressure and ozone with decreased lung function. A negative trend between UFPs and forced expiratory volume in the first second was observed. We concluded that short-term exposure to UFPs was associated with cardiovascular health in adult subjects in the urban areas of northern Taiwan.