Circular RNA METTL9 contributes to neuroinflammation following traumatic brain injury by complexing with astrocytic SND1.

BACKGROUND: Circular RNAs (circRNAs) are highly enriched in the central nervous system and have been implicated in neurodegenerative diseases. However, whether and how circRNAs contribute to the pathological processes induced by traumatic brain injury (TBI) has not been fully elucidated. METHODS: We conducted a high-throughput RNA sequencing screen for well-conserved, differentially expressed circRNAs in the cortex of rats subjected to experimental TBI. Circular RNA METTL9 (circMETTL9) was ultimately identified as upregulated post-TBI and further characterized by RT-PCR and agarose gel electrophoresis, Sanger sequencing, and RNase R treatment. To examine potential involvement of circMETTL9 in neurodegeneration and loss of function following TBI, circMETTL9 expression in cortex was knocked-down by microinjection of a shcircMETTL9 adeno-associated virus. Neurological functions were evaluated in control, TBI, and TBI-KD rats using a modified neurological severity score, cognitive function using the Morris water maze test, and nerve cell apoptosis rate by TUNEL staining. Pull-down assays and mass spectrometry were conducted to identify circMETTL9-binding proteins. Co-localization of circMETTL9 and SND1 in astrocytes was examined by fluorescence in situ hybridization and immunofluorescence double staining. Changes in the expression levels of chemokines and SND1 were estimated by quantitative PCR and western blotting. RESULTS: CircMETTL9 was significantly upregulated and peaked at 7 d in the cerebral cortex of TBI model rats, and it was abundantly expressed in astrocytes. We found that circMETTL9 knockdown significantly attenuated neurological dysfunction, cognitive impairment, and nerve cell apoptosis induced by TBI. CircMETTL9 directly bound to and increased the expression of SND1 in astrocytes, leading to the upregulation of CCL2, CXCL1, CCL3, CXCL3, and CXCL10, and ultimately to enhanced neuroinflammation. CONCLUSION: Altogether, we are the first to propose that circMETTL9 is a master regulator of neuroinflammation following TBI, and thus a major contributor to neurodegeneration and neurological dysfunction.

Thoracic perivascular adipose tissue inhibits VSMC apoptosis and aortic aneurysm formation in mice via the secretome of browning adipocytes.

Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.

Successful application of continuous renal replacement therapy in a very low birth weight neonate with acute kidney injury.

Diagnosis and treatment process during hospitalization.

KCa3.1 in diabetic kidney disease.

PURPOSE OF REVIEW: Diabetic kidney disease (DKD) is a significant health concern. Innovative strategies to prevent or limit the progression of DKD are urgently needed due to the limitation of existing treatments. KCa3.1, a potassium channel, is involved in a range of biological processes from cell survival to cell death. This review summarizes the current knowledge on the pathophysiological functions of the KCa3.1 channel, specifically its involvement in maintaining mitochondrial function. More specifically, the therapeutic potential of targeting KCa3.1 in DKD is systematically discussed in the review. RECENT FINDINGS: Mitochondrial dysfunction contributes to the development and progression of DKD. Accumulating evidence indicates that KCa3.1 dysregulation plays a crucial role in mitochondrial dysfunction, in addition to driving cellular activation, proliferation and inflammation. Recent studies demonstrate that KCa3.1 deficiency improves diabetes-induced mitochondrial dysfunction in DKD, which is attributed to modulation of mitochondrial quality control through mitigating the altered mitochondrial dynamics and restoring abnormal BNIP3-mediated mitophagy. SUMMARY: Based on its role in fibrosis, inflammation and mitochondrial dysfunction, pharmacological inhibition of KCa3.1 may offer a promising alternative for the treatment of DKD. Due to its safety profile in humans, the repurposing of senicapoc has the potential to expedite an urgently needed new drug in DKD.

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease.

Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices only defers the development of kidney failure. Death, transplantation, or dialysis are the consequences of kidney failure, resulting in a significant burden on the health system. Hence, innovative therapeutic strategies are urgently needed due to the limitations of current interventions. Photobiomodulation (PBM), a form of non-thermal light therapy, effectively mitigates mitochondrial dysfunction, reactive oxidative stress, inflammation, and gut microbiota dysbiosis, all of which are inherent in CKD. Preliminary studies suggest the benefits of PBM in multiple diseases, including CKD. Hence, this review will provide a concise summary of the underlying action mechanisms of PBM and its potential therapeutic effects on CKD. Based on the findings, PBM may represent a novel, non-invasive and non-pharmacological therapy for CKD, although more studies are necessary before PBM can be widely recommended.

[Effect of Rehmanniae Radix Praeparata on energy metabolism in prefrontal cortex of rats with attention deficit hyperactivity disorder based on "static Yin and dynamic Yang" theory].

The present study investigated the effect of Rehmanniae Radix Praeparata(RRP) on the energy metabolism of prefrontal cortex(PFC) of spontaneously hypertensive rats with attention deficit hyperactivity disorder(ADHD) based on the "static Yin and dynamic Yang" theory.Thirty spontaneously hypertensive male rats aged 3 weeks were randomly divided into a model group, a methylphenidate(MPH) group(2 mg·kg~(-1)), and an RRP group(2.4 g·kg~(-1)).Wistar-Kyoto(WKY) male rats of the same age were assigned to the normal group.Rats were treated with corresponding drugs twice per day, and those in the model group and the normal group received the same volume of 0.9% sodium carboxymethyl cellulose(CMC-Na) solution by gavage.The open-field test was performed to evaluate the spontaneous and impulsive behaviors of rats before treatment and on the 4~(th) week after treatment.Four weeks after treatment, PFC was isolated and mitochondria were prepared.The content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in the PFC was determined by high-performance liquid chromatography(HPLC), and energy charge(EC) was calculated.The parameters related to mitochondrial respiratory function were measured by the Clark oxygen electrode, specifically, state 3 respiration(ST3), state 4 respiration(ST4), and respiratory control rate(RCR).Enzymatic activities of succinate dehydrogenase(SDH), cytochrome C oxidase(COX), Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase were measured by chemical colorimetry.Mitochondrial permeability transition pore(mPTP) opening was measured by spectrophotometry.Protein expression of glucose transporter 1(GLUT1) and GLUT3 in PFC was tested by Western blot.Compared with the results in the model group, RRP could significantly reduce the total distance of movement, vertical times, and distance in the central area in the open field test(P<0.05 or P<0.01), increase the content of ATP and EC, decrease the content of AMP(P<0.05), elevate ST3 and RCR(P<0.05), potentiate activities of SDH, COX, Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase(P<0.05 or P<0.01), inhibit the opening of mPTP, and increase the expression levels of GLUT1 and GLUT3 proteins(P<0.05).It was inferred that RRP could inhibit hyperacti-vity and impulsivity by improving the energy metabolism disorder in PFC of ADHD rats, and its mechanism may be related to the improvement of mitochondrial respiratory function, potentiation of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, and mitochondrial respiratory enzymes, inhibition of the opening of mPTP, and up-regulation of the expression of glucose transporter proteins.This study initially reveals the biological connotation of the "static Yin and dynamic Yang" theory in ADHD.

RIPK3 blockade attenuates kidney fibrosis in a folic acid model of renal injury.

Renal fibrosis is common to all forms of progressive kidney disease. However, current therapies to limit renal fibrosis are largely ineffective. Phosphorylation of receptor-interacting serine/threonine-protein kinase (RIPK) 3 has been recently suggested to be a key regulator of the pyrin domain containing 3 (NLRP3) inflammasome, which provides new insights into mechanisms of chronic kidney disease (CKD). However, the specific effect of RIPK3 on renal cortical fibrosis has not been fully understood. To study the function of RIPK3, both genetic ablation and pharmacological inhibition of RIPK3 (dabrafenib) were used in the study. Our studies identify that RIPK3 promotes renal fibrosis via the activation of the NLRP3 inflammasome in a mouse model of folic acid-induced nephropathy. Both interventional strategies decreased the renal fibrotic response, and beneficial effects converged on the NLRP3 inflammasome. This study demonstrates a role for RIPK3 as the mediator of renal fibrosis via the upregulation of inflammasome activation. Dabrafenib, as an inhibitor of RIPK3, may be an effective treatment to limit the progression of the tubulointerstitial fibrosis.

Exposure to ethephon compromises endometrial decidualization in mice during early pregnancy via GPR120.

Exposure to ethephon (ETH), a plant growth regulator commonly used for several purposes, can potentially decrease sperm numbers and viability. Occasional findings regarding ETH effects on female reproduction during early pregnancy have also been reported. During early pregnancy, endometrial decidualization is a critical event for embryo implantation and pregnancy maintenance. Thus, we aimed to explore the effect and mechanism of ETH on endometrial decidualization both in vivo and in vitro. Mice were gavaged with 0 and 285 mg/kg b.w. ETH from gestational days (GD)1 until sacrifice, whereas pseudopregnant mice from pseudopregnant day 1 (PPD-1) until PPD-8. Primary mouse endometrial stromal cells (mESCs) received 640 ug/ml ETH and added E2 and P4 to induce decidualization. Results indicated female albino CD1 mice exposed to high dose of ETH (285 mg/kg b.w.) by oral gavage, the number of embryo implantation sites on GD6 and GD8 were significantly decreased, the levels of serum E2 and P4 on GD8 were significantly decreased. Compared with the control group, the decidualization response artificially induced by corn oil in pseudopregnant mice and by E2 and P4 in primary mouse endometrial stromal cells (mESCs) was weakened in the high dose of ETH treated group. The high dose, 285 mg/kg b.w ETH treated group altered the expression of endometrial decidual markers on GD6 and GD8. The triglyceride and fatty acid metabolism-related genes were significantly increased after female albino CD1 mice exposed to high does, 285 mg/kg b.w ETH on GD6 and GD8. GPR120 was substantially reduced after ETH treatment. When overexpression of GPR120, the compromised decidualization induced by ETH treatment was rescued. Furthermore, molecular docking presented Thr234 and His251 of GPR120 as preferred binding sites for ETH. Mutation of these two sites rescued the compromised decidualization induced by ETH. In conclusion, we demonstrated that ETH exposure could impair decidualization during early pregnancy. GPR120 expression and binding between GPR120 and ETH are crucial for impaired decidualization mediated via ETH.

The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease.

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

Effect of surgical treatment on prognosis in preterm infants with obstructive hydrocephalus. / æ—©äº§å„¿æ¢—é˜»æ€§è„‘ç§¯æ°´å¤–ç§‘æ²»ç–—ä¸Žé¢„åŽçš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the effect of surgical treatment on prognosis in preterm infants with obstructive hydrocephalus. METHODS: A retrospective analysis was performed on the medical data of 49 preterm infants with obstructive hydrocephalus. According to the treatment regimen, they were divided into two groups: surgical treatment (n=12) and conservative treatment (n=37). The drainage methods, drainage complications, and eventual shunt outcome were analyzed in the surgical treatment group. The two groups were compared in terms of the etiology of hydrocephalus and prognosis. RESULTS: Among the 49 preterm infants with obstructive hydrocephalus, severe intracranial hemorrhage (37 cases; 76%) and central nervous system infection (10 cases, 20%) were the main causes of hydrocephalus. There was no significant difference in the composition of etiology between the two groups (P>0.05). In the surgical treatment group, 4 infants were treated with ventriculosubgaleal shunt and 8 were treated with Ommaya reservoir. One infant had secondary infection and 8 infants eventually underwent ventriculoperitoneal shunt. The surgical treatment group had a significantly higher survival rate than the conservative treatment group (P<0.05). As for the 37 preterm infants with severe intracranial hemorrhage, the surgical treatment group had a significantly higher proportion of infants with normal neurodevelopment than the conservative treatment group (P<0.05). As for the 10 preterm infants with central nervous system infection, neurodevelopmental abnormalities were observed in each of the two groups. CONCLUSIONS: Surgical treatment can improve the survival rate of preterm infants with obstructive hydrocephalus and the prognosis of preterm infants with severe intracranial hemorrhage.

Metformin attenuates folic-acid induced renal fibrosis in mice.

Progressive tubulointerstitial fibrosis has been recognized as a common pathological process that leads to the progression of all chronic kidney disease (CKD). Innovative strategies are needed to both prevent and treat CKD. Inflammatory and fibrotic signaling pathways play central roles in the progression of CKD regardless of aetiology. Hence, targeting inflammatory and fibrotic responses holds promise to limit renal fibrosis. Metformin has been the most prescribed glucose-lowering medicine worldwide, and its potential for many other therapeutic applications is also being explored intensively. Increasing evidence indicates metformin may limit renal fibrosis. However, the exact mechanisms whereby metformin limits renal injury are not fully understood. The anti-fibrotic effects of metformin, independent of improved glycaemic control was examined in a folic acid-induced mouse model of nephropathy for 14 days. Human proximal tubular cells (HK2 cells) exposed to TGF-ß1 were used in in vitro models to examine mechanistic pathways. Folic acid induced nephropathy was associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV collagen, fibronectin and TGF-ß1 compared to control groups, which were partially attenuated by metformin treatment. In vitro studies confirmed that metformin inhibited TGF-ß1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells. These results suggest that metoformin attenuates folic acid-induced renal interstitial fibrogenesis through TGF-ß1 signaling pathways.

KCa3.1: a new player in progressive kidney disease.

PURPOSE OF REVIEW: Hypertension and hyperglycaemia are major risk factors that result in chronic kidney disease (CKD). Achievement of blood pressure goals, optimal control of blood glucose levels and the use of agents to block the renin-angiotensin-aldosterone system slow the progression of CKD. However, not all patients are benefited by these interventions and novel strategies to arrest or reverse the pathological processes inherent in CKD are needed. The therapeutic potential of targeting KCa3.1 in CKD will be discussed in this review. RECENT FINDINGS: Blockade of KCa3.1 ameliorates activation of renal fibroblasts in diabetic mice by inhibiting the transforming growth factor-ß1/small mothers against decapentaplegic pathway. A concomitant reduction in nuclear factor-κB activation in human proximal tubular cells under diabetic conditions has been observed. Advanced glycosylated endproducts induce both protein expression and current density of KCa3.1, which, in turn, mediates migration and proliferation of vascular smooth muscle cells via Ca²âº-dependent signalling pathways. SUMMARY: Studies have clearly demonstrated a causal role of chronic hyperglycaemia and hypertension in the development of CKD. However, a large proportion of patients develop end-stage kidney disease despite strict glycaemic control and the attainment of recommended blood pressure goals. Therefore, it is essential to identify and validate novel targets to reduce the development and progression of CKD. Recent findings demonstrate that genetic deletion or pharmacologic inhibition of KCa3.1 significantly reduces the development of diabetic nephropathy in animal models. However, the consequences of blockade of KCa3.1 in preventing and treating established diabetic nephropathy in humans warrants further study.

Thioredoxin-interacting protein mediates dysfunction of tubular autophagy in diabetic kidneys through inhibiting autophagic flux.

Thioredoxin-interacting protein (TXNIP) expression is ubiquitous and is induced by a variety of cellular stresses, including high intracellular glucose. TXNIP is associated with activation of oxidative stress and tubulointerstitial fibrosis in diabetic nephropathy. Autophagy is a major pathway that delivers damaged proteins and organelles to lysosomes to maintain cellular homeostasis. This study aimed to investigate the dysregulation of autophagy and the regulation of TXNIP on autophagy in renal proximal tubular cells (PTCs) under diabetic conditions. The formation of autophagosomes was measured using transmission electron microscopy, and LC3-II, and the effectiveness of autophagic clearance was determined by p62 expression in diabetic kidney and in human PTCs exposed to high glucose (HG). The results collectively demonstrated increased expression of TXNIP, LC3/LC3-II and p62 in renal tubular cells of mice with diabetic nephropathy and in cultured human PTCs exposed to HG (30 mM/l) for 48 h compared with control. The formation of autophagic vacuoles was increased in HG-induced cells. Furthermore, silencing of TXNIP by siRNA transfection reduced autophagic vacuoles and the expression of LC3-II and p62 in human PTCs exposed to HG compared with control and partially reversed the accumulation of LC3-II and p62 induced by bafilomycin A1 (50 nM/l), a pharmacological inhibitor of autophagy which blocks the fusion of autophagosomes with lysosomes and impairs the degradation of LC3-II and p62. Collectively, these results suggest that hyperglycemia leads to dysfunction of autophagy in renal tubular cells and decreases autophagic clearance. HG-induced overexpression of TXNIP may contribute to the dysfunction of tubular autophagy in diabetes.

Role of the potassium channel KCa3.1 in diabetic nephropathy.

There is an urgent need to identify novel interventions for mitigating the progression of diabetic nephropathy. Diabetic nephropathy is characterized by progressive renal fibrosis, in which tubulointerstitial fibrosis has been shown to be the final common pathway of all forms of chronic progressive renal disease, including diabetic nephropathy. Therefore targeting the possible mechanisms that drive this process may provide novel therapeutics which allow the prevention and potentially retardation of the functional decline in diabetic nephropathy. Recently, the Ca2+-activated K+ channel KCa3.1 (KCa3.1) has been suggested as a potential therapeutic target for nephropathy, based on its ability to regulate Ca2+ entry into cells and modulate Ca2+-signalling processes. In the present review, we focus on the physiological role of KCa3.1 in those cells involved in the tubulointerstitial fibrosis, including proximal tubular cells, fibroblasts, inflammatory cells (T-cells and macrophages) and endothelial cells. Collectively these studies support further investigation into KCa3.1 as a therapeutic target in diabetic nephropathy.

KCa3.1 mediates activation of fibroblasts in diabetic renal interstitial fibrosis.

BACKGROUND: Fibroblast activation plays a critical role in diabetic nephropathy (DN). The Ca2+-activated K+ channel KCa3.1 mediates cellular proliferation of many cell types including fibroblasts. KCa3.1 has been reported to be a potential molecular target for pharmacological intervention in a diverse array of clinical conditions. However, the role of KCa3.1 in the activation of myofibroblasts in DN is unknown. These studies assessed the effect of KCa3.1 blockade on renal injury in experimental diabetes. METHODS: As TGF-ß1 plays a central role in the activation of fibroblasts to myofibroblasts in renal interstitial fibrosis, human primary renal interstitial fibroblasts were incubated with TGF-ß1+/- the selective inhibitor of KCa3.1, TRAM34, for 48 h. Two streptozotocin-induced diabetic mouse models were used in this study: wild-type KCa3.1+/+ and KCa3.1-/- mice, and secondly eNOS-/- mice treated with or without a selective inhibitor of KCa3.1 (TRAM34). Then, markers of fibroblast activation and fibrosis were determined. RESULTS: Blockade of KCa3.1 inhibited the upregulation of type I collagen, fibronectin, α-smooth muscle actin, vimentin and fibroblast-specific protein-1 in renal fibroblasts exposed to TGF-ß1 and in kidneys from diabetic mice. TRAM34 reduced TGF-ß1-induced phosphorylation of Smad2/3 and ERK1/2 but not P38 and JNK MAPK in interstitial fibroblasts. CONCLUSIONS: These results suggest that blockade of KCa3.1 attenuates diabetic renal interstitial fibrogenesis through inhibiting activation of fibroblasts and phosphorylation of Smad2/3 and ERK1/2. Therefore, therapeutic interventions to prevent or ameliorate DN through targeted inhibition of KCa3.1 deserve further consideration.

A self-supervised spatio-temporal attention network for video-based 3D infant pose estimation.

General movement and pose assessment of infants is crucial for the early detection of cerebral palsy (CP). Nevertheless, most human pose estimation methods, in 2D or 3D, focus on adults due to the lack of large datasets and pose annotations on infants. To solve these problems, here we present a model known as YOLO-infantPose, which has been fine-tuned, for infant pose estimation in 2D. We further propose a self-supervised model called STAPose3D for 3D infant pose estimation based on videos. We employ multi-view video data during the training process as a strategy to address the challenge posed by the absence of 3D pose annotations. STAPose3D combines temporal convolution, temporal attention, and graph attention to jointly learn spatio-temporal features of infant pose. Our methods are summarized into two stages: applying YOLO-infantPose on input videos, followed by lifting these 2D poses along with respective confidences for every joint to 3D. The employment of the best-performing 2D detector in the first stage significantly improves the precision of 3D pose estimation. We reveal that fine-tuned YOLO-infantPose outperforms other models tested on our clinical dataset as well as two public datasets MINI-RGBD and YouTube-Infant dataset. Results from our infant movement video dataset demonstrate that STAPose3D effectively comprehends the spatio-temporal features among different views and significantly improves the performance of 3D infant pose estimation in videos. Finally, we explore the clinical application of our method for general movement assessment (GMA) in a clinical dataset annotated as normal writhing movements or abnormal monotonic movements according to the GMA standards. We show that the 3D pose estimation results produced by our STAPose3D model significantly boost the GMA prediction performance than 2D pose estimation. Our code is available at github.com/wwYinYin/STAPose3D.

Platelet-Rich Plasma Intrauterine Infusion as Assisted Reproduction Technology (ART) to Combat Repeated Implantation Failure (RIF): A Systematic Review and Meta-Analysis.

Background: Repeated implantation failure (RIF) is considered one of the major challenges facing clinician in assisted reproduction technologies (ART) despite the significant advances that have been made in this field. Platelet rich plasma (PRP), also known as autologous conditioned plasma, is a protein concentrate with anti-inflammatory and pro-regenerative characteristics. The use of PRP in women undergoing ART has been studied in the past, with varying degrees of success. The goal of this trial was to see if injecting PRP into the uterus improves pregnancy outcomes in women receiving ART. Methods: PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials were among the databases searched (CENTRAL), from 2015 to 2021. The pooled estimates were calculated using a meta-analysis with a random-effects model. There were 14 studies with a total of 1081 individuals (549 cases and 532 controls). Results: There was no difference in miscarriage rates between women who got PRP and those who received placebo (P≤0.90). Chemical pregnancy (P≤0.00), clinical pregnancy (P ≤0.001), and implantation rate (P≤ 0.001) were all significantly higher in women. Endometrial thickness increased in women who got PRP vs women who received placebo after the intervention (P ≤0.001). Conclusion: PRP may be an alternate therapeutic approach for individuals with thin endometrium and RIF, according to the findings of this comprehensive study. To determine the subgroup that would benefit the most from PRP, more prospective, big, and high-quality randomized controlled trials (RCTs) are needed.

Multiplex Assessment of Serum Chemokines CCL2, CCL5, CXCL1, CXCL10, and CXCL13 Following Traumatic Brain Injury.

Chemokines may promote neuroinflammation following traumatic brain injury (TBI), thereby exacerbating secondary injury. This study was designed to investigate the contributions of chemokines (CCL2, CCL5, CXCL1, CXCL10, and CXCL13) to TBI severity and clinical outcome. Peripheral blood was drawn from 92 TBI patients on admission, and 40 controls were recruited. Serum concentrations of CCL2, CCL5, CXCL1, CXCL10, and CXCL13 on admission were measured by ELISA. Preoperative clinical severity was evaluated using the Glasgow Coma Scale (GCS), and clinical outcome at 90 days post-TBI was evaluated using the Glasgow Outcome Scale (GOS). The associations were evaluated by calculating Spearman's correlation coefficients. A binary logistic regression model was used to identify clinicodemographic factors influencing outcome, and ROC curves were constructed. Serum concentrations of CCL2, CCL5, CXCL1, CXCL10, and CXCL13 were elevated significantly after TBI and negatively correlated with GCS and GOS scores except CCL5. CCL2 may be considered as an independent predictor to predict severity and outcome. Moreover, combination of GCS score, CCL2, and CXCL10 can be a better assessment prognosis of moderate and severe TBI.

Empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of vascular smooth muscle cells.

SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE-/- mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.