Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

Clinical analysis of 125I seed implantation combined with Apatinib in the treatment of locally advanced lung cancer: A case series.

This clinical analysis of 125I seed implantation combined with Apatinib in the treatment of locally advanced lung cancer with negative driving genes was retrospectively performed on 19 patients in the Department of Thoracic Surgery, Tianjin First Central Hospital, from January 2018 to May 2019. Twelve cases were treated with Apatinib after 125I implantation, while the other seven were treated with 125I implantation only. IL-2R, IL-6 and TNF-α before and after the treatment, imaging changes every two months and related side effects were recorded. After the treatment, IL-2R, IL-6 and TNF-α of all the patients decreased in the first month, which was more obvious in combined therapy patients; the total effective rate in combined therapy patients was significantly higher than the others. There were no fatal complications, and all the side-effects were well tolerated by medical treatment. It shows that 125I seed implantation combined with Apatinib is effective and safe in the treatment of locally advanced lung cancer.

Double-barreled defense: dual ent-miltiradiene synthases in most rice cultivars.

Rice (Oryza sativa) produces numerous diterpenoid phytoalexins that are important in defense against pathogens. Surprisingly, despite extensive previous investigations, a major group of such phytoalexins, the abietoryzins, were only recently reported. These aromatic abietanes are presumably derived from ent-miltiradiene, but such biosynthetic capacity has not yet been reported in O. sativa. While wild rice has been reported to contain such an enzyme, specifically ent-kaurene synthase-like 10 (KSL10), the only characterized ortholog from O. sativa (OsKSL10), specifically from the well-studied cultivar (cv.) Nipponbare, instead has been shown to make ent-sandaracopimaradiene, precursor to the oryzalexins. Notably, in many other cultivars, OsKSL10 is accompanied by a tandem duplicate, termed here OsKSL14. Biochemical characterization of OsKLS14 from cv. Kitaake demonstrates that this produces the expected abietoryzin precursor ent-miltiradiene. Strikingly, phylogenetic analysis of OsKSL10 across the rice pan-genome reveals that from cv. Nipponbare is an outlier, whereas the alleles from most other cultivars group with those from wild rice, suggesting that these also might produce ent-miltiradiene. Indeed, OsKSL10 from cv. Kitaake exhibits such activity as well, consistent with its production of abietoryzins but not oryzalexins. Similarly consistent with these results is the lack of abietoryzin production by cv. Nipponbare. Although their equivalent product outcome might suggest redundancy, OsKSL10 and OsKSL14 were observed to exhibit distinct expression patterns, indicating such differences may underlie retention of these duplicated genes. Regardless, the results reported here clarify abietoryzin biosynthesis and provide insight into the evolution of rice diterpenoid phytoalexins. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00167-3.

Oryzalexin S biosynthesis: a cross-stitched disappearing pathway.

Rice produces many diterpenoid phytoalexins and, reflecting the importance of these natural products in this important cereal crop plant, its genome contains three biosynthetic gene clusters (BGCs) for such metabolism. The chromosome 4 BGC (c4BGC) is largely associated with momilactone production, in part due to the presence of the initiating syn-copalyl diphosphate (CPP) synthase gene (OsCPS4). Oryzalexin S is also derived from syn-CPP. However, the relevant subsequently acting syn-stemarene synthase gene (OsKSL8) is not located in the c4BGC. Production of oryzalexin S further requires hydroxylation at carbons 2 and 19 (C2 and C19), presumably catalyzed by cytochrome P450 (CYP) monooxygenases. Here it is reported the closely related CYP99A2 and CYP99A3, whose genes are also found in the c4BGC catalyze the necessary C19-hydroxylation, while the closely related CYP71Z21 and CYP71Z22, whose genes are found in the recently reported chromosome 7 BGC (c7BGC), catalyze subsequent hydroxylation at C2α. Thus, oryzalexin S biosynthesis utilizes two distinct BGCs, in a pathway cross-stitched together by OsKSL8. Notably, in contrast to the widely conserved c4BGC, the c7BGC is subspecies (ssp.) specific, being prevalent in ssp. japonica and only rarely found in the other major ssp. indica. Moreover, while the closely related syn-stemodene synthase OsKSL11 was originally considered to be distinct from OsKSL8, it has now been reported to be a ssp. indica derived allele at the same genetic loci. Intriguingly, more detailed analysis indicates that OsKSL8(j) is being replaced by OsKSL11 (OsKSL8i), suggesting introgression from ssp. indica to (sub)tropical japonica, with concurrent disappearance of oryzalexin S production. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-022-00092-3.

Nano-Sized PtRu/C Electrocatalyst With Separated Phases and High Dispersion Improves Electrochemical Performance of Hydrogen Oxidation Reaction.

Alloys and core-shell nanoparticles have recently received enormous attention which opened up new avenues for highly active catalysts. Despite considerable advances in this field, the majority of proposed approaches suffer from either complicated procedures or unstable structures, severely hindering their practical applications. Here, we successfully synthesized alloy electrocatalyst with separated phases, PtRu alloy nanoparticles robustly supported by carbon matrix (PtRu/C), using a convenient two-step solvothermal method. The constructed PtRu/C at different NaOH contents (0-1.25 mmol) were compared and electrochemical activity were evaluated by the hydrogen oxidation reaction (HOR). In contrast, the homogeneous distribution and minimum average size of Ru and Pt nanoparticles on carbon, appeared at approximately 4 nm, proving that PtRu/C-0.75 possessed abundant accessible active sites. The catalytic activities and the reaction mechanism were studied via electrochemical techniques. PtRu/C-0.75 has excellent activity due to its unique electronic structure and efficient charge transfer, with the largest j0 value of 3.68 mA cm-2 in the HOR.

A novel circular RNA, hsa_circ_0030998 suppresses lung cancer tumorigenesis and Taxol resistance by sponging miR-558.

Circular RNAs (circRNAs) are single-stranded RNAs which form a covalently closed continuous loop. Although originally shown to be non-protein-coding, some circRNAs can give rise to micropeptides. circRNAs have also been shown to play essential regulatory roles in a variety of developmental and disease processes. In a previous study, hsa_circ_0030998 was identified as a circRNA downregulated in lung cancer, but its potential implications and mechanisms in lung cancer were not addressed. Here, we showed that overexpressing circ_0030998 decreased proliferation, migration, and invasion of lung cancer cells, while also dampening resistance to Taxol, a classical antitumor drug. Depleting circ_0030998 reversed these phenotypic effects. A high circ_0030998 expression was correlated with a high survival rate in lung cancer patients. Additionally, we found circ_0030998 could downregulate miR-558 expression, serving as a microRNA sponge. In conclusion, our data support that hsa_circ_0030998 can slow down the progression of lung cancer by targeting miR-558 and suppress malignant phenotypes such as proliferation, migration, and invasion progression of lung cancer cells. Therefore, we highlight that circ_0030998 could be a novel tumor suppressor of lung cancer.

Islet transplantation ameliorates diabetes-induced testicular interstitial fibrosis and is associated with inhibition of TGF-ß1/Smad2 pathway in a rat model of type 1 diabetes.

Islet transplantation (IT) is considered the most effective endocrine replacement therapy for diabetes mellitus (DM). Studies have demonstrated that IT can repair testicular structural injury caused by inflammatory and oxidative stress in a diabetic rat model. However, highly effective exogenous antioxidant and anti-inflammatory drugs can achieve this effect. Testicular interstitial fibrosis caused by long-term hyperglycemia is however difficult to reverse or recover. Thus far, there are no effective drugs that prevent or relieve testicular interstitial fibrosis. Therefore, it is necessary to explore the potential benefit of IT on testicular interstitial fibrosis induced by DM and its underlying molecular mechanisms. In the present study, Wistar rats were used to establish a DM model by intraperitoneal injection of streptozotocin. The diabetic models then underwent IT or received insulin treatment after 12 weeks. IT was more effective than insulin treatment in ameliorating diabetic-induced testicular interstitial fibrosis, Leydig cells apoptosis, testosterone deficiency and poor sperm motility. IT and insulin treatment both significantly inhibited the upregulation of TGF-ß1 and phosphorylated Smad2 in DM, with IT being more effective than insulin. The present study's findings proved that IT effectively protects diabetic-induced testicular interstitial fibrosis probably by inhibiting the TGF-ß1/Smad2 signaling pathway, which offers hope in male patients with DM complicating with testicular interstitial fibrosis.

Integrated Metabolomics and Transcriptomics Analyses Reveal the Molecular Mechanisms Underlying the Accumulation of Anthocyanins and Other Flavonoids in Cowpea Pod (Vigna unguiculata L.).

As an important vegetable crop of the legume family, cowpea (Vigna unguiculata L.) is grown widely for its tender pod with good taste and nutrition. The purple cowpea pods attract more attention mainly for the eye-catching color and health-promoting ingredients. Initially, large quantities of two major anthocyanins (delphinidin 3-O-glucoside and cyanidin 3-O-glucoside) and nine kinds of flavonoids (most are quercetin-based flavonol glycosides) were separated and identified from purple cowpea pod by ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry. To study them systematically, two representative cowpea cultivars with a drastic difference in anthocyanin accumulation were further analyzed by the integration of metabolomics and transcriptomics. A total of 56 differentially accumulated metabolites and 4142 differentially expressed genes were identified, respectively. On the basis of the comprehensive analysis of multiomic data, it was shown that VuMYB90-1, VuMYB90-2, VuMYB90-3, VuCPC, VuMYB4, and endogenous bHLH and WD40 proteins coordinately control anthocyanin and flavonoid accumulation via transcriptional regulation of structural genes in purple cowpea pod.

[Clinical observation on the target therapy of rh-endostin, combined with chemotherapy in advanced non-small cell lung cancer.].

BACKGROUND: The chemotherapy of advanced non-small cell lung cancer is in a Bottleneck. The target therapy of Anti-angiogenesis gradually shows an advantage in the therapy of patients with advanced NSCLC. To investigate the short-term efficacy, safety and the quality of life of the target therapy of rh-Endostin combined with chemotherapy in patients with advanced NSCLC. METHODS: Sixty-two advanced NSCLC patients were randomly divided into either the trial group with chemotherapy plus rh-Endostin or control group with chemotherapy alone. The efficacy and toxicity were evaluated after 2 cycles according to RECIST criteria. RESULTS: The trial groups efficiency rate was 46.87%, while the control group was 26.66%, there was no significant differences of two groups (Chi-square=1.912, P=0.166). The clinical benefit rate was 81.25% in the trial group and 53.33% in control group. There was significant difference of the clinical benefit rate between the trial group and the control group (Chi-square=4.3185, P=0.0377). The score of quality of life in the trial group was significantly higher than that the control group after the treatment (Chi-square=11.233, P=0.0008). There was no significant difference of incidence of toxicities between the trial group and the control group (P>0.05). CONCLUSIONS: Rh-Endostin combined with chemotherapy was effective, reasonable, safe and well tolerated for advanced NSCLC.