Impaired arginine/ornithine metabolism drives severe HFMD by promoting cytokine storm.

Introduction: The Hand, Foot and Mouth Disease (HFMD), caused by enterovirus 71 infection, is a global public health emergency. Severe HFMD poses a significant threat to the life and well-being of children. Numerous studies have indicated that the occurrence of severe HFMD is associated with cytokine storm. However, the precise molecular mechanism underlying cytokine storm development remains elusive, and there are currently no safe and effective treatments available for severe HFMD in children. Methods: In this study, we established a mouse model of severe HFMD to investigate the molecular mechanisms driving cytokine storm. We specifically analyzed metabolic disturbances, focusing on arginine/ornithine metabolism, and assessed the potential therapeutic effects of spermine, an ornithine metabolite. Results: Our results identified disturbances in arginine/ornithine metabolism as a pivotal factor driving cytokine storm onset in severe HFMD cases. Additionally, we discovered that spermine effectively mitigated the inflammatory injury phenotype observed in mice with severe HFMD. Discussion: In conclusion, our findings provide novel insights into the molecular mechanisms underlying severe HFMD from a metabolic perspective while offering a promising new strategy for its safe and effective treatment.

Reversal of the tamoxifen­resistant breast cancer malignant phenotype by proliferation inhibition with bromosulfonamidine amino­podophyllotoxin.

One of the lignans isolated from plants within the genus Podophyllum is podophyllotoxin (PPT). PPT and its derivatives are pharmacologically active compounds with potential antiproliferative properties in several kinds of tumors. Although these compounds have been used to treat other malignancies, no PPT derivative-based chemotherapeutic agent has been used to cure tamoxifen (TAM)-resistant breast cancer in clinical trials, to the best of our knowledge. Thus, using TAM-resistant breast cancer as a disease model, the present study assessed the effects of a recently synthesized PPT derivative, bromosulfonamidine amino-PPT (BSAPPT), on TAM-resistant breast cancer. Using the tamoxifen-resistant breast cancer cell model (MCF-7/TAMR) in vitro, Cell Counting Kit-8 and colony formation assays were adopted to evaluate the effect of BSAPPT on cell proliferation. Cell apoptosis and cell cycle assays were used to assess the influence of BSAPPT on cell apoptosis and the cell cycle in MCF-7/TAMR. The targets of the potential mechanism of action were analyzed by RT-qPCR and western blotting. The present study demonstrated that BSAPPT suppressed MCF-7/TAMR cell proliferation in a dose-dependent manner. By modulating the level of expression of genes linked to both apoptosis and the cell cycle, BSAPPT triggered MCF-7/TAMR cells to undergo apoptosis and prevented them from entering the cell cycle. Consequently, BSAPPT blocked these cells from proliferating, thereby halting the malignant advancement of TAM-resistant breast cancer. Therefore, these findings indicate that new therapeutic agents involving BSAPPT may be developed to facilitate the treatment of TAM-resistant breast cancer.

Apolipoprotein A1 is associated with osteocalcin and bone mineral density rather than high-density lipoprotein cholesterol in Chinese postmenopausal women with type 2 diabetes mellitus.

Objective: Disturbances in high-density lipoprotein cholesterol (HDL-c) metabolic pathways can affect bone metabolism, which may rely on the particle function of apolipoprotein rather than HDL-c levels. This study aimed to evaluate the correlation of serum HDL-c and apolipoprotein A1 (APOA1) with bone metabolism in Chinese postmenopausal women with type 2 diabetes mellitus (T2DM). Method: A total of 1,053 participants with complete data were enrolled and separated into three groups based on the HDL-c and APOA1 tertiles. The trained reviewer collected demographic and anthropometric information. Bone turnover markers (BTMs) were determined by standard methods. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. Results: Overall, the prevalence of osteoporosis was 29.7%. Groups with higher APOA1 have a remarkably more elevated level of osteocalcin (OC), L1-L4 BMD, and T-score across the APOA1 tertiles. APOA1 presented a positive correlation with OC (r = 0.194, p < 0.001), L1-L4 BMD (r = 0.165, p < 0.001), and T-score (r = 0.153, p < 0.001) rather than HDL-c. Meanwhile, APOA1 remained independently associated with OC (ß = 0.126, p < 0.001), L1-L4 BMD (ß = 0.181, p < 0.001), and T-score (ß = 0.180, p < 0.001) after adjustment for confounding factors. APOA1 is also shown to be independently correlated with osteoporosis after adjustment for confounding factors, and the OR (95%CI) was 0.851 (0.784-0.924). In contrast, there was no significant association between HDL-c and osteoporosis. Furthermore, APOA1 seemed to have the largest areas under the curve (AUC) for osteoporosis. The AUC (95% CI) of APOA1 identifying osteoporosis was 0.615 (0.577-0.652). The optimal cut-off value of APOA1 was 0.89 g/L (sensitivity: 56.5%, specificity: 67.9%). Conclusion: APOA1 is independently associated with OC, L1-L4 BMD, and osteoporosis rather than HDL-c in Chinese postmenopausal women with T2DM.

Diterpenes from oriental tobacco Nicotiana tabacum 'YNOTBS1' and their bioactivities.

Seven diterpenes including two new seco-cembranoid basmanoids A (1) and B (2), and two new labdane basmadanes A (3) and B (4), and three known compounds (-)-dehydro-nor-ambreinolid (5), (13E)-8-hydroxy-13-labden-12-one (6), and 14,15,16-dinor-7-oxolabda-8-ene-13-oic acid (7) were isolated from oriental tobacco Nicotiana tabacum 'YNOTBS1'. Compounds 1-3 and 5 showed anti-tobacco mosaic virus (TMV) activity with inhibition rates in the range of 30-69% at the concentration of 1 mg/mL. However, none of them exhibited any inhibitory effects against nitric oxide (NO) production in LPS and IFN-γ-induced RAW 264.7 murine macrophages and anti-proliferative activities against cancer cell lines SMMC-7721 and A-549.

Occurrence and dietary exposure assessment of pentachlorophenol in livestock, poultry, and aquatic foods marketed in Guangdong Province, China: Based on food monitoring data from 2015 to 2018.

As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in the Guangdong Province (GD) of China, and the resultant dietary exposure have not been elucidated. To address this gap, 3,100 samples from seven food categories, including beef, pork, mutton, offals, broilers, hen eggs, and farmed freshwater fish, marketed throughout four geographical regions of GD, were collected from 2015 to 2018. Gas chromatography coupled with mass spectrometry was employed to detect PCP levels in these food matrices. PCP was found in all food categories, but the average contamination levels were low, ranging from 0.40 µg/kg wet weight (ww) (hen eggs) to 5.85 µg/kg ww (offals). However, higher concentrations of PCP were detected (P < 0.05) in animal source food from the North region. Additionally, a temporal declining trend was observed in this four-year consecutive survey. The estimated human dietary exposure of PCP to population groups, including the general population and subgroups (male and female, children, and adults), was found to be far below the permissible daily intake (3 µg/kg body weight). Therefore, the health impacts of PCP should be correspondingly low for local residents, based on current toxicological knowledge. Regional exposure patterns varied due to different extents of contamination in the four areas, and pork, broilers, and freshwater fish were the major sources of dietary PCP exposure. PRACTICAL APPLICATION: As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in Guangdong Province of China, and the resultant dietary exposure have not been elucidated. In this study, we conducted an in-depth investigation on the occurrence of PCP in major foodstuff categories, including beef, pork, mutton, broilers, offals, hen eggs, and farmed freshwater fish, marketed in all 21 prefecture-level divisions of Guangdong Province, in order to provide integral insights for regulatory authorities.

Rapid analysis of cyclamate in foods and beverages by gas chromatography-electron capture detector (GC-ECD).

A rapid method for determination of sodium cyclamate in foods and beverages was developed. Sodium cyclamate was converted to N,N-dichloridecyclohexylamine by reaction with sodium hypochlorite under acid condition. N,N-dichloridecyclohexylamine was subsequently extracted by n-hexane and determined by gas chromatography. Conditions such as derivatization time, the concentration of sodium hypochlorite and sulphuric acid were optimised. Amino acids, aliphatic amines, and food additives such as preservatives, dyes and sweeteners showed no interference for quantification of cyclamate. The correlation coefficient of calibration curve was 0.9993 in the range of 5.0-250mg/L. The limits of detection (LOD) and limits of quantification (LOQ) were calculated as three or ten times the signal-to-noise ratio (S/N), respectively. The LOD and LOQ for yellow wine and fruit juice were 0.05 and 0.2mg/L, respectively. The LOD and LOQ for cake and preserved fruit were 0.25 and 0.8mg/kg, respectively. The intra-day and inter-day RSD were 0.28% and 1.1% (n=5), respectively. The method was successfully applied for determination of cyclamate in yellow wine, cake, fruit juice and preserved fruit. This method was simple, fast, and sensitive. It was suitable for the determination of cyclamate in foods and beverages for safety and quality control inspections.