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Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg(−1) ·d(−1), ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 μM), which was attenuated by co-treatemnt with puerarin (100 μM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 μM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

Aims To examine the association between 24 literature‐based single nucleotide polymorphisms and diabetic kidney disease in Chinese people with type 2 diabetes. Methods and results Twenty‐four candidate diabetic kidney disease‐susceptible single nucleotide polymorphisms were genotyped in 208 participants with type 2 diabetes and diabetic kidney disease and 200 participants with type 2 diabetes without diabetic kidney disease (case and control groups, respectively), together with 206 healthy participants using MassARRAY. Rs11643718 in the SLC12A3 gene was associated with diabetic kidney disease in the recessive model after adjusting for confounding factors, such as age and gender (adjusted odds ratio 2.056, 95% CI 1.120–3.776; P = 0.020). Meta‐analyses further confirmed the association (P = 0.002). In addition, participants with the GG genotype had worse renal function and more albuminuria than those with the AA+AG genotype (P < 0.05). Renal section immunohistochemistry was conducted in participants with type 2 diabetes, diabetic kidney disease and AA+AG or GG genotypes and in participants with glomerular minor lesions. Together with data from the Nephroseq database, it was shown that the abundance of SLC12A3 was reduced in patients with the GG genotype, while elevated expression of SLC12A3 was associated with better renal function. In addition, rs10951509 and rs1345365 in ELMO1, which were determined to be in high linkage disequilibrium by SHEsis software, were also associated with diabetic kidney disease (adjusted P = 0.010 and 0.015, respectively). Conclusions The G allele and GG genotype of SLC12A3 rs11643718 are associated with the development of diabetic kidney disease in a Chinese population with type 2 diabetes., What's new? Many diabetic kidney disease (DKD)‐susceptible single‐nucleotide polymorphims (SNPs) in type 2 diabetes have been identified; however, the relationship between some SNPs and DKD is still controversial. The effect of several SNPs on DKD in Chinese populations with type 2 diabetes is also unclear.This study found that the G allele and GG genotype in SLC12A3 rs11643718, as well as the G allele and GG+AG genotype in ELMO1 rs10951509 and rs1345365, may be risk factors for DKD in Chinese type 2 diabetes populations.Analysing these genotypes in people with type 2 diabetes will be helpful in identifying populations with high risk of DKD.

Glucagon-like peptide 1 (GLP-1) can promote islet β-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving β-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment. Liraglutide significantly enhanced the function of MSCs to preserve islet β-cells by reducing glucose level at 30 minutes post glucose challenge and increasing the contents and secretion of insulin by islet β-cells in severe diabetic NOD mice. Infusion with MSCs significantly reduced insulitis scores, but increased the frequency of splenic Tregs, accompanied by reducing the levels of plasma IFN-γ and TNF-α and elevating the levels of plasma IL-10 and transforming growth factor-β1 (TGF-β1) in NOD mice. Although Liraglutide mitigated MSC-mediated changes in the frequency of Tregs and the levels of plasma IL-10, Liraglutide significantly increased the levels of plasma TGF-β1 in severe diabetic NOD mice. Therefore, our findings suggest that Liraglutide may enhance the therapeutic efficacy of MSCs in treatment of severe type 1 diabetes.

The article analyzed the existing problems and deficiencies in the electromagnetic induction heating method in the production process of the current plastics machinery. Furthermore a solution is proposed to adopt rotational scanning heating via improving the power of the current heating controllers. Meanwhile, a systematic engineering approach is put forward, which is proved to be stable and reliable through industrial field trial.

With the variational series resonance load circuit, people can design a kind of intermediate frequency induction heating power supply for the Injection molding machine. The article has analysed the basic operation principle of the variational half bridge series resonance inverter, and introduce the main circuit structure and switch tube driver protection of induction heating power supply, and also raised the engineering design method. The frequency of operation of this electromagnetism induction heating power supply is 20 kHz with the output power of 10 KW, and it can be used in the injection molding machine and to heat the charging barrel of comminutors. The experimental results show that this power can provide good sine-wave current, the performance of which has met the design requirements, and the power supply has been operated in industrial field.

AIMS: To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes. METHODS: A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA-2, insulin, thyroid globulin or thyroid peroxidase, or high-risk HLA-DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF-1alpha (MODY3) and neuroD1/beta2 (MODY6) genes were screened using the single-strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Within the cohort, we found one patient with a novel mutation, R321H (CGC-->CAC) in exon 5 of the HNF-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/beta2 gene, and two patients with autoantibodies to SOX13. CONCLUSIONS: Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.