High level of thyroid peroxidase antibodies as a detrimental risk of pregnancy outcomes in euthyroid women undergoing ART: A meta-analysis.

Thyroid autoimmunity (TAI) triggered by genetic and epigenetic variation occurs mostly in women of reproductive age. TAI is described mainly by positivity of anti-thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). TPO-Ab, but not TG-Ab, was suggested to be associated with pregnancy outcome in euthyroid women undergoing assisted reproductive technology (ART), but their results are conflicting. This meta-analysis was performed to decide whether the presence of TPO-Ab-in a concentration dependent manner-correlates with the success of ART. A systematic literature search was performed in the PubMed, Web of Science, and EMBASE databases for relevant articles published from January 1999 to April 2022, and these studies focused on the effect of TAI on pregnancy outcomes of women who underwent in vitro fertilization, intracytoplasmic sperm injection and intrauterine insemination and met the inclusion criteria: (i) the studies were prospective or retrospective study; (ii) all patients undergoing ART were tested for thyroid-related antibodies; (iii) the assessed ART outcomes included miscarriage rate (MR) or delivery rate (DR). The exclusion criteria were: (i) female congenital uterine malformation, chromosomal diseases and other infectious diseases; (ii) overt hypothyroidism or pre-existing thyroid disease; (iii) thrombus tendency. We divided the included patients into three groups according to the TPO-Ab threshold they defined: (i) TPO-Ab (-), threshold <34 IU/mL; (ii) TPO-Ab-34, threshold >34 IU/mL; (iii) TPO-Ab-100, threshold >100 IU/mL. We then extracted necessary relevant data, including MR and DR. Egger's test was used to evaluate the risk of publication bias. This meta-analysis included a total of 7 literatures involving 7466 patients with TAI (-) and 965 patients with TAI (+) and revealed that there was no significant difference between group TPO-Ab-34 and group TPO-Ab (-) in MR [risk ratio (RR): 0.61 (0.35, 1.08), p = 0.09] and DR [RR: 0.97 (0.83, 1.13), p = 0.69]. By contrast, compared to TPO-Ab (-) group, TPO-Ab-100 patients showed markedly higher MR [RR: 2.12 (1.52, 2.96), p = 0.0046], and lower DR [RR: 0.66 (0.49, 0.88), p < 0.0001] with high degree of statistical significance. This meta-analysis suggests that, for euthyroid patients, high level of TPO-Ab (>100 IU/mL) could adversely influence the pregnancy outcome of ART.

A single administration of FGF2 after renal ischemia-reperfusion injury alleviates post-injury interstitial fibrosis.

BACKGROUND: Despite lack of clinical therapy in acute kidney injury (AKI) or its progression to chronic kidney disease (CKD), administration of growth factors shows great potential in the treatment of renal repair and further fibrosis. At an early phase of AKI, administration of exogenous fibroblast growth factor 2 (FGF2) protects against renal injury by inhibition of mitochondrial damage and inflammatory response. Here, we investigated whether this treatment attenuates the long-term renal interstitial fibrosis induced by ischemia-reperfusion (I/R) injury. METHODS: Unilateral renal I/R with contralateral nephrectomy was utilized as an in vivo model for AKI and subsequent CKD. Rats were randomly divided into four groups: Sham-operation group, I/R group, I/R-FGF2 group and FGF2-3D group. These groups were monitored for up to 2 months. Serum creatinine, inflammatory response and renal histopathology changes were detected to evaluate the role of FGF2 in AKI and followed renal interstitial fibrosis. Moreover, the expression of vimentin, α-SMA, CD31 and CD34 were examined. RESULTS: Two months after I/R injury, the severity of renal interstitial fibrosis was significantly attenuated in both of I/R-FGF2 group and FGF2-3D group, compared with the I/R group. The protective effects of FGF2 administration were associated with the reduction of high-mobility group box 1 (HMGB1)-mediated inflammatory response, the inhibition of transforming growth factor beta (TGF-ß1)/Smads signaling-induced epithelial-mesenchymal transition and the maintenance of peritubular capillary structure. CONCLUSIONS: A single dose of exogenous FGF2 administration 1 h or 3 days after reperfusion inhibited renal fibrogenesis and thus blocked the transition of AKI to CKD. Our findings provided novel insight into the role of FGF signaling in AKI-to-CKD progression and underscored the potential of FGF-based therapy for this devastating disease.

Chitosan oligosaccharide attenuates acute kidney injury and renal interstitial fibrosis induced by ischemia-reperfusion.

Acute kidney injury (AKI) and renal interstitial fibrosis are global clinical syndromes associated with high morbidity and mortality. Renal ischemia-reperfusion (I/R) injury, which commonly occurs during surgery, is one of the major causes of AKI. Nevertheless, an efficient therapeutic approach for AKI and the development of renal interstitial fibrosis is still lacking due to its elusive pathogenetic mechanism. Here, we showed that chitosan oligosaccharide (COS), a natural oligomer polysaccharide degraded from chitosan, significantly attenuates I/R-induced AKI and maintains glomerular filtration function by inhibiting oxidative stress, mitochondrial damage, and excessive endoplasmic reticulum stress both in vitro and in vivo. In addition, long-term administration of COS can also attenuate the proliferation of myofibroblasts, mitigate extra cellular matrix deposition, and thus inhibit the transition of AKI to chronic kidney disease through participating in metabolic and redox biological processes. Our findings provide novel insights into the protective role of COS against acute kidney injury.

The immunity-related GTPase IRGC mediates interaction between lipid droplets and mitochondria to facilitate sperm motility.

The immunity-related GTPases (IRGs) belong to the interferon-inducible GTPase protein family, which mediates cell autonomous and innate immunity response to intracellular pathogens. Yet, the cellular and physiological function of IRGC, a member of the IRG subfamily, has not been elucidated. Here, we show that testis-specific IRGC is specifically and highly expressed in mature spermatozoa and is required for sperm motility. IRGC induction results in the clustering of lipid droplets and initiation of their physical contact with mitochondria. When examining clinical semen samples, IRGC expression is significantly lower in asthenozoospermia patients relative to healthy individuals. These unique effects of IRGC identify it as an important player in sperm motility, and show the potential of lipid metabolism-targeting therapeutic intervention aimed at controlling asthenozoospermia.

Decoding microRNAs in autism spectrum disorder.

Autism spectrum disorder (ASD)-a congenital mental disorder accompanied by social dysfunction and stereotyped behaviors-has attracted a great deal of attention worldwide. A combination of genetic and environmental factors may determine the pathogenesis of ASD. Recent research of multiple ASD models indicates that microRNAs (miRNAs) play a central role at the onset and progression of ASD by repressing the translation of key mRNAs in neural development and functions. As such, miRNAs show great potential to serve as biomarkers for ASD diagnosis or prognosis and therapeutic targets for the treatment of ASD. In this review, we discuss the regulatory mechanisms by which miRNAs influence ASD phenotypes through various in vivo and in vitro models, including necropsy specimens, animal models, cellular models, and, in particular, induced pluripotent stem cells derived from patients with ASD. We then discuss the potential of miRNA-based therapeutic strategies for ASD currently being evaluated in preclinical studies.

Paeoniflorin Suppresses Rheumatoid Arthritis Development via Modulating the Circ-FAM120A/miR-671-5p/MDM4 Axis.

Paeoniflorin is an active ingredient derived from Paeonia, which has an anti-inflammatory effect. However, the potential role and basis of paeoniflorin in rheumatoid arthritis (RA) are indistinct. Cell viability, cycle distribution, migration, and invasion were evaluated via Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. The contents of inflammatory cytokines were examined using enzyme-linked immunosorbent assay (ELISA). RNA expression levels were determined via qRT-PCR and western blot. The targeting relationship between miR-671-5p and circ-FAM120A (hsa_circ_0003972) or murine double minute 4 (MDM4) was validated via dual-luciferase reporter assay. Paeoniflorin restrained proliferation, migration, invasion, and inflammation and accelerated cell cycle arrest in RA fibroblast-like synoviocytes (RA-FLSs). Circ-FAM120A was boosted in RA synovial tissues and RA-FLSs. Circ-FAM120A upregulation, miR-671-5p knockdown, or MDM4 augmentation reversed the repressive effect of paeoniflorin on RA-FLS progression. Moreover, paeoniflorin attenuated RA-FLS progression by regulating the circ-FAM120A/miR-671-5p/MDM4 axis. Paeoniflorin inhibited RA-FLS proliferation, mobility, and inflammation and triggered cell cycle arrest via mediating the circ-FAM120A/miR-671-5p/MDM4 pathway.