Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

The impact of vitamin D on the etiopathogenesis and the progression of type 1 and type 2 diabetes in children and adults.

Diabetes is a common chronic metabolic disease with complex causes and pathogenesis. As an immunomodulator, vitamin D has recently become a research hotspot in the occurrence and development of diabetes and its complications. Many studies have shown that vitamin D can reduce the occurrence of diabetes and delay the progression of diabetes complications, and vitamin D can reduce oxidative stress, inhibit iron apoptosis, promote Ca2+ influx, promote insulin secretion, and reduce insulin resistance. Therefore, the prevention and correction of vitamin D deficiency is very necessary for diabetic patients, but further research is needed to confirm what serum levels of vitamin D3 are maintained in the body. This article provides a brief review of the relationship between vitamin D and diabetes, including its acute and chronic complications.

Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents.

The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. However, neither approved vaccines nor drugs are available for ZIKV. In this study, we describe the design, synthesis and the anti-ZIKV activities of a series of anthraquinone analogs. Most of the newly synthesized compounds demonstrated moderate to excellent potency against ZIKV. Among all, compound 22, showed the most potent anti-ZIKV activity (EC50 value from 1.33 µM to 5.72 µM) with low cytotoxicity (CC50＞50 µM) in multiple cellular model. Importantly, 22 significantly improved the survival of ZIKV-infected mice (Ifnar1-/-), alleviated ZIKV-associated pathological damages and suppressed the excessive inflammatory response and pyroptosis induced by ZIKV in vivo and in vitro. Furthermore, the molecular docking simulation analysis and the surface plasmon resonance results demonstrated the direct binding between 22 and ZIKV RdRp, and the mechanistic study revealed that 22 suppressed viral RNA synthesis by ZIKV NS5 in cells. Taken together, this study highlights that 22 may be a novel anti-ZIKV drug candidate and provides treatment options for ZIKV-associated diseases.

A new chromone from Kandelia candel endophytic fungus Aspergillus sp. ZJ-68.

One chromone (1), together with four known alkaloids, were isolated from the mangrove endophytic fungus Aspergillus sp. ZJ-68. Their structures were elucidated by a combination of HRESIMS and NMR spectroscopic analyses. Compound 1 showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 4.094 ± 0.8 µM, which was better than positive drug indomethacin (IC50=35.8 ± 0.5 µM).

Interaction Between Apolipoprotein M Gene Single-Nucleotide Polymorphisms and Obesity and its Effect on Type 2 Diabetes Mellitus Susceptibility.

This study investigated the correlation of four single nucleotide polymorphisms (SNPs) in Apolipoprotein M (ApoM) with the risk of type 2 diabetes mellitus (T2DM) and effects of the interactions of this gene and obesity. The effects of SNP and obesity interaction on T2DM was examined by generalized multifactor dimensionality reduction (GMDR) combined with the logistic regression model. T2DM patient-control haplotype was analyzed in silico using the haplotype analysis algorithm SHEsis. The rs805296-C allele or 724-del allele indicted high risk of T2DM. The incidence of T2DM in individuals with rs805296-C allele polymorphism (TC + CC) was higher than those without (TT), adjusted OR (95%CI) = 1.29 (1.10-1.66) (p < 0.001). Moreover, the individuals with 724-delallele have a higher risk of T2DM compared to those with 724-ins variants, adjusted OR (95%CI) = 1.66 (1.40-2.06), p < 0.001. GMDR analysis suggested that the interaction model composed of the two factors, rs805296 and obesity, was the best model with statistical significance (P value from sign test [Psign]=0.0107). The T2DM risk in obese individuals having TC or CC genotype was higher than non-obese individuals with TT genotype (OR = 2.38, 95% CI = 1.58-3.53). Haplotype analysis suggests that rs805297-C and rs9404941-C alleles haplotype indicate high risk of T2DM, OR (95%CI) = 1.62 (1.29-2.16), p < 0.001. Our results suggested that rs805296 and 724-del minor allele of ApoM gene, interaction of rs805296 and obesity, rs805297-C and rs9404941-C alleles haplotype were indicators of high T2DM risk.