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We aimed to explore the mechanism underlying microRNA-23-5p from exosomes (exo-miR-23-5p) of BMSCs in rheumatoid arthritis (RA). The candidate related genes of miR-23-5p were screened in RA by bioinformatics analysis through gain- and loss-function method along with analysis of histopathological changes in mice and RAC2 expression as well as the level of pro-inflammatory factors. In vivo RA model was established to detect miR-23-5p’s effect on RA. miR-23-5p level was significantly reduced in RA cells and RAC2 was highly expressed. Expression of RAC2 was inhibited and targeted by miR-23-5p in RA. Exo-miR-23-5p treatment effectively alleviated joint destruction, reduced inflammatory factor secretion in tissues and serum, as well as decreased RAC2 expression in RA model. In conclusion, the miR-23-5p in the BMSC-exo delays the inflammatory response in RA, indicating that it might be a new target for treating RA.

The disturbance of intestinal microorganisms and the exacerbation of type 2 diabetes (T2D) are mutually influenced. In this study, the effect of exopolysaccharides (EPS) from Lactobacillus plantarum JY039 on the adhesion of Lactobacillus paracasei JY062 was investigated, as well as their preventive efficacy against T2D. The results showed that the EPS isolated from L. plantarum JY039 effectively improved the adhesion rate of L. paracasei JY062 to Caco-2 cells (1.8 times) and promoted the proliferation of L. paracasei JY062. In the mice experiment, EPS, L. paracasei JY062 and their complex altered the structure of the intestinal microbiota, which elevated the proportion of Bifidobacterium, Faecalibaculum, while inversely decreasing the proportion of Firmicutes, Muribaculaceae, Lachnospiraceae and other bacteria involved in energy metabolism (p < 0.01; p < 0.05); enhanced the intestinal barrier function; promoted secretion of the gut hormone peptide YY (PYY) and glucagon-like peptide-1 (GLP-1); and reduced inflammation by balancing pro-inflammatory factors IL-6, TNF-α and anti-inflammatory factor IL-10 (p < 0.01; p < 0.05). These results illustrate that EPS and L. paracasei JY062 have the synbiotic potential to prevent and alleviate T2D.

Objectives: To retrospectively evaluate a multidisciplinary cooperative first aid model for the treatment of patients with pelvic and multiple fractures in the emergency department. Methods: The records of patients with pelvic fractures complicated with multiple fractures treated in our hospital from February 2020 to April 2021 were selected, of which 34 patients received conventional trauma first aid mode (control group) and 34 patients received multidisciplinary joint first aid mode (study group). We compared pelvic function (Majeed functional score) and fracture reduction outcomes, as well as serum inflammatory factor levels and complication rates after treatment between the two groups. Results: The Majeed score in the study group (90.15 ± 6.83) was higher than that in the control group (75. 47 ± 5.35), and the differences were statistically significant (P<0.05). The value for combined excellent and good rates of fracture reduction in the study group (85.29%, 29/34) was significantly higher than that in the control group (58.82%, 20/34), and the difference was statistically significant(P<0.05). We found similar levels of TNF-a and IL-6 between the two groups at admission (P>0.05); however, the serum levels of TNF-a and IL-6 in the study group were lower than those in the control group on the fifth day after admission, and the difference was statistically significant (P<0.05 or P<0.01). The incidence of complications in the study group (17.64%, 6/34) was significantly lower than that in the control group (61.76%, 21/34), the difference was statistically significant (P<0.05). Conclusion: The multidisciplinary cooperative first aid model for the treatment of patients with pelvic and multiple fractures can effectively shorten the treatment time, increase the excellent functional rehabilitation rate, inhibit the release of inflammatory factors, and reduce the incidence of complications (such as infections), when compared to the conventional trauma emergency system. doi: https://doi.org/10.12669/pjms.38.3.5014 How to cite this:Han Y, Peng G, Liu L, Xie X. Multidisciplinary cooperative first aid model for the treatment of patients with pelvic and multiple fractures. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.5014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

BackgroundHypothermic circulatory arrest (HCA) in aortic arch surgery has a significant risk of neurological injury despite the newest protective techniques and strategies. Nitric oxide (NO) could exert a protective role, reduce infarct area and increase cerebral perfusion. This study aims to investigate the possible neuroprotective effects of NO administered in the oxygenator of selective antegrade cerebral perfusion (SCP) during HCA.MethodsThirty male SD adult rats (450–550 g) underwent cardiopulmonary bypass (CPB), cooling to 22°C body core temperature followed by 30 min of HCA. Rats were randomized to receive SCP or SCP added with NO (20 ppm) administered through the oxygenator (SCP-NO). All animals underwent CPB-assisted rewarming to a target temperature of 35°C in 60 min. At the end of the experiment, rats were sacrificed, and brain collected. Immunofluorescence analysis was performed in blind conditions.ResultsNeuroinflammation assessed by allograft inflammatory factor 1 or ionized calcium-binding adapter molecule 1 expression, a microglia activation marker was lower in SCP-NO compared to SCP (4.11 ± 0.59 vs. 6.02 ± 0.18%; p &lt; 0.05). Oxidative stress measured by 8oxodG, was reduced in SCP-NO (0.37 ± 0.01 vs. 1.03 ± 0.16%; p &lt; 0.05). Brain hypoxic area extent, analyzed by thiols oxidation was attenuated in SCP-NO (1.85 ± 0.10 vs. 2.74 ± 0.19%; p &lt; 0.05). Furthermore, the apoptotic marker caspases 3 was significantly reduced in SCP-NO (10.64 ± 0.37 vs. 12.61 ± 0.88%; p &lt; 0.05).ConclusionsNitric oxide administration in the oxygenator during SCP and HCA improves neuroprotection by decreasing neuroinflammation, optimizing oxygen delivery by reducing oxidative stress and hypoxic areas, finally decreasing apoptosis.

Abstract Background: The migration, proliferation, and inflammatory factor secretion of vascular smooth muscle cells (VSMCs) are involved in the important pathological processes of several vascular occlusive diseases, including coronary atherosclerosis (CAS). IL-1β, as a bioactive mediator of VSMC synthesis and secretion, can promote the pathological progress of CAS. In this study, we further explored the underlying molecular mechanisms by which IL-1β regulates VSMC migration, invasion.Methods: We pretreated A7r5 and HASMC with IL-1β for 24 hours, and measured the expression of IL-1β, PCNA, cyclin D1, MMP2 and MMP9 in the cells by Western blotting. Cell migration and invasion ability were measured by Transwell and wound healing assays. Cell viability was measured by an MTT assay. Results: We found that IL-1β up-regulated the expression of proliferation-related proteins (PCNA and Cyclin D1) in A7r5 and HASMC, and induces the secretion of MMP2 and MMP9, promotes cell invasion and migration. In addition, in A7r5 and HASMCs treated with IL-1β, the expression of Ang2 increased in a time-dependent manner, transfection with si-Ang2 suppressed cell migration and invasion, with down-regulated MMP2 and MMP9 expression. In parallely, we further found that the p38-MAPK pathway is activated in cells induced by IL-1β, p38-MAPK inhibitors can down-regulate the expression of Ang2. Conclusions: These data demonstrated that IL-1β promotes A7r5 and HASMC migration and invasion via the p38-MAPK/Ang2 pathway.

Whether berberine mediates its anti-inflammatory and blood sugar and lipid-lowering effects solely by adjusting the structure of the gut microbiota or by first directly regulating the expression of host pro-inflammatory proteins and activation of macrophages and subsequently acting on gut microbiota, is currently unclear. To clarify the mechanism of berberine-mediated regulation of metabolism, we constructed an obese mouse model using SPF-grade C57BL/6J male mice and conducted a systematic study of liver tissue pathology, inflammatory factor expression, and gut microbiota structure. We screened the gut microbiota targets of berberine and showed that the molecular mechanism of berberine-mediated treatment of metabolic syndrome involves the regulation of gut microbiota structure and the expression of inflammatory factors. Our results revealed that a high-fat diet (HFD) significantly changed mice gut microbiota, thereby probably increasing the level of toxins in the intestine, and triggered the host inflammatory response. The HFD also reduced the proportion of short-chain fatty acid (SCFA)-producing genes, thereby hindering mucosal immunity and cell nutrition, and increased the host inflammatory response and liver fat metabolism disorders. Further, berberine could improve the chronic HFD-induced inflammatory metabolic syndrome to some extent and effectively improved the metabolism of high-fat foods in mice, which correlated with the gut microbiota composition. Taken together, our study may improve our understanding of host-microbe interactions during the treatment of metabolic diseases and provide useful insights into the action mechanism of berberine.

We investigated the application effect of different concentrations of platelet-rich plasma (PRP) combined with quadriceps training on cartilage repair of knee osteoarthritis. Data of 37 patients with knee osteoarthritis (KOA) treated in our hospital (November 2019–February 2021) were retrospectively analyzed and the patients were divided into low concentration group (LCG) (n = 12), medium concentration group (MCG) (n = 12), and high concentration group (HCG) (n = 13) according to the order of admission. All patients received quadriceps training. Three groups above received knee injection of PRP, and the platelet concentrations were 1000–1400 × 109/L, 1400–1800 × 109/L, and 1800–2100 × 109/L, respectively. Articular cartilage thickness of the medial and lateral femur, knee joint function scores, inflammatory factor levels, and matrix metalloproteinases (MMPs) levels were compared. After treatment, compared with the MCG and HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the LCG was obviously lower ( P < 0.05 ). At 2 months after treatment (T3), compared with the HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the MCG was obviously higher ( P < 0.05 ), without remarkable difference in articular cartilage thickness of the medial and lateral femur of the healthy side among three groups ( P > 0.05 ). After treatment, compared with the LCG, knee joint function scores of the MCG and HCG were obviously better ( P < 0.001 ). Compared with the HCG, the knee function score at T3 in the MCG was obviously better ( P < 0.001 ). After treatment, compared with the LCG, inflammatory factor levels and levels of MMPs in the MCG and HCG were obviously lower ( P < 0.05 ). Compared with the HCG, inflammatory factor levels and levels of MMPs at T3 in the MCG were obviously lower ( P < 0.05 ). PRP combined with quadriceps training can accelerate cartilage repair of patients with KOA and reduce inflammatory factor levels and levels of MMPs, but the treatment effect of PRP depends on platelet concentration, with the best range of 1400–1800 × 109/L. Too high or too low platelet concentrations will affect recovery of knee function.

IntroductionThe impact of bovine mastitis on animal husbandry is great huge. It is anincurable an incurable disease mainly characterized by milk and pathological changes in milk and the mammary gland, which causescause reduced yield and quality of milk, but. Unfortunately, the use of antibiotics to combat mastitis affects the production of milk, so it is urgent to find additional therapeutic molecules for mastitis treatment.Material and methodsIn this study, we analyzed the protection provided by hyperoside (HYP) in a model of mastitis in vivo and explored its functional mechanism in mouse mammary epithelial cells (mMECs) by overexpression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3).ResultsOur results showed that HYP at 12.5, 25 and 50 mg/kg prevented the inflammatory response induced in lipopolysaccharide (LPS)-stimulated micemouse mammary glands as well as inflammatory cytokine production, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-8. The protection provided by HYP was also correlated with the reduction of NLRP3 signaling pathway protein levels in vivo. However, overexpression of NLRP3 reversed the effects of HYP on the NLRP3 inflammasome, cell viability and inflammatory factor levels in LPS-stimulated mMECs.ConclusionsIn summary, this study showed that HYP inhibited LPS-stimulated symptoms of breast inflammation by regulating expression of inflammatory cytokines and inhibiting the NLRP3 signaling pathway.

Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.

Radiation-induced brain injury is a common complication of brain irradiation that eventually leads to irreversible cognitive impairment. Evidence has shown that the gut microbiome may play an important role in radiation-induced cognitive function. However, the effects of gut microbiota on radiation-induced brain injury (RIBI) remain poorly understood. Here we studied the link between intestinal microbes and radiation-induced brain injury to further investigate the effects of intestinal bacteria on neuroinflammation and cognitive function. We first verified the differences in gut microbes between male and female mice and administered antibiotics to C57BL/6 male mice to deplete the gut flora and then expose mice to radiation. We found that depletion of intestinal flora after irradiation may act as a protective modulator against radiation-induced brain injury. Moreover, we found that pretreatment with depleted gut microbes in RIBI mice suppressed brain pro-inflammatory factor production, and high-throughput sequencing analysis of mouse feces at 1-month postirradiation revealed microbial differences. Interestingly, a proportion of Verrucomicrobia Akkermansia showed partial recovery. Additionally, short-chain fatty acid treatments increased neuroinflammation in the radiation-induced brain injury model. Although a further increase in cognitive function was not observed, brain injury was aggravated in whole-brain irradiated mice to some extent. The protective effects of depleted intestinal flora and the utilization of the brain-gut axis open new avenues for development of innovative therapeutic strategies for radiation-induced brain injury.