Chinese Medical Sciences Journal最新文献

Objective

To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism.

Methods

Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight •d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting.

Results

Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention.

Conclusion

DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

Objective

Aberrant expression of ATP binding cassette subfamily B member 1 (ABCB1) plays a key role in several cancers. However, influence of G protein coupled receptor family C group 5 type A (GPRCSA)-regulated ABCB1 expression on lung adenocarcinoma proliferation remains unclear. Therefore, this study investigated the effect of GPRC5A regulated ABCB1 expression on the proliferation of lung adenocarcinoma.

Methods

ABCBI expressions in lung adenocarcinoma cell lines, human lung adenocarcinoma tissues, and tracheal epithelial cells and lung tissues of GPRC5A knockout mice and wild-type mice were analyzed with RT-PCR, Western blot, or immunohistochemical analysis. Cell counting kit-8 assay was performed to analyze the sensitivity of tracheal epithelial cells from GPRC5A knockout mice to chemotherapeutic agents. Subcutaneous tumor formation assay was performed to confirm whether down-regulation of ABCBI could inhibit the proliferation of lung adenocarcinoma in vivo. To verify the potential regulatory relationship between GPRCS A and ABCB1, immunofluorescence and immunoprecipitation assays were performed.

Results

ABCB1 expression was up-regulated in lung adenocarcinoma cell lines and human lung adenocarcinoma tissues. ABCBI expression in the tracheal epithelial cells and lung tissues of GPRC5A deficient mice was higher than that in the wild type mice. Tracheal epithelial cells of GPRC5A knockout mice were much more sensitive to tariquidar and doxorubicin than those of GPRC5A wild type mice. Accordingly, 28 days after injection of the transplanted cells, the volume and weight of lung tumor in ABCBI knockout cell-transplanted GPRCS A^-/C57BL/6 mice were significantly smaller than those in wild type cell-transplanted mice (P = 0.0043, P = 0.0060). Furthermore, immunofluorescence and immunoprecipitation assays showed that GPRC5A regulated ABCBI expression by direct binding.

Conclusion

GPRC5A reduces lung adenocarcinoma proliferation via inhibiting ABCBI expression. The pathway by which GPRC5A regulates ABCBI expression needs to be investigated.

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.

Objective

As primary Sjogren's syndrome (pSS) primarily affects the salivary glands, saliva can serve as an indicator of the glands’ pathophysiology and the disease's status. This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis.

Methods

The discovery set contained 49 samples (24 from pSS and 25 from age- and gender-matched healthy controls [HCs]) and the validation set included 25 samples (12 from pSS and 13 from HCs). Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio. Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition (DIA) strategy on a 2D LC–HRMS/MS platform to reveal differential proteins. The crucial proteins were verified using DIA analysis and annotated using gene ontology (GO) and International Pharmaceutical Abstracts (IPA) analysis. A prediction model for SS was established using random forests.

Results

A total of 1,963 proteins were discovered, and 136 proteins exhibited differential representation in pSS patients. The bioinformatic research indicated that these proteins were primarily linked to immunological functions, metabolism, and inflammation. A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm, and was validated as the predictive biomarkers exhibiting good performance with area under the curve (AUC) of 0.817 for discovery set and 0.882 for validation set.

Conclusions

The candidate protein panel discovered may aid in pSS diagnosis. Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients. DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Objective

Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.

Methods

The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity. Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 – 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 – 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 – 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 – 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 – 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 – 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 – 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 – 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: –82.97; 95%CI: -109.04––56.90; P < 0.001).

Conclusions

Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

Objective

To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein (ABI3BP) on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway.

Methods

The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-Sta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-Sta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels.

Results

The VSV-GFP-infected BJ-Sta cell model was successfully established. Efficient knockdown of ABI3BP in BJ-Sta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 – 3.5 times (P<0.01) and 2.2 – 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection.

Conclusions

Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication, and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.