Background: Chronic low back pain (LBP) is associated with changes in the thoracolumbar fascia (TLF) structure. Gua Sha is a traditional manual therapy that can relieve LBP, but there is a lack of clinical evidence on whether it can affect fascial properties. Objectives: To investigate the immediate effects of Gua Sha on TLF thickness and functional parameters in healthy adults. Methods: In this pilot randomized controlled trial, 24 healthy participants were randomly assigned to a Gua Sha group (n = 12) or a control group (n = 12). The intervention group received a single 15-minute Gua Sha session, while the control group rested in a prone position. Outcomes, including TLF thickness, tissue hardness, pressure pain threshold , skin temperature, and lumbar flexibility, were measured before and immediately after the intervention. Results: Compared to the control group, the Gua Sha group showed a significant reduction in bilateral TLF thickness (right: mean difference -0.40 mm, 95% CI -0.71 to -0.09, p = 0.017; left: -0.36 mm, 95% CI -0.68 to -0.05, p = 0.027). Significant improvements were also observed in skin temperature (p < 0.001), left-side pressure pain threshold (p <0.01), and lumbar flexibility (p <0.001). Tissue hardness slightly increased post-intervention, but not significantly. Conclusion: A single Gua Sha session reduced TLF thickness and enhanced lumbar flexibility in healthy adults, supporting its potential as a fascia-targeted intervention. Further studies in LBP populations are warranted.

In the present study, we aimed to investigate the antioxidant and therapeutic protective effects of carvacryl acetate (CAA) on Mitochondrial damage of cerebral ischemia-reperfusion through mitochondrial transcription factor A (TFAM) signaling molecules.SD rats were used to establish the middle cerebral artery occlusion (MCAO) model in vivo, and PC12 cells were stimulated with H2O2 in vitro. Longa neurological score and triphenyltetrazolium chloride (TTC) staining was used to observe the ischemic infarction. Transmission electron microscope (TEM) was used to observe the mitochondria. Reactive Oxygen Species/ Superoxide Dismuptase/Malondialdehyde/Adenosine Triphosphate (ROS/SOD/MDA/ATP) detection kit was used to detect. RT-qPCR was used to detect the mRNA level of target gene and mitochondrial DNA (mtDNA) copy number changes. Immunofluorescence and Western blot were used to detect the expression of protein. After oxidative stress in the MCAO model of SD rats, the neurological score increased, the volume of ischemic area of cerebral infarction increased, the morphology of nerve cells in brain tissue and PC12 cells was disordered, the mitochondria appeared vacuolated, the contents of ROS and MDA increased, and the activity of SOD decreased. Oxidative stress causes mitochondrial dysfunction, resulting in the reduction of mtDNA copy number and the decreased expression of TFAM in brain tissue nerve cells and PC12 cells, which in turn affects mitochondrial transcription biogenesis and decreases the expression of POLRMT and TFB2M molecules. CAA promotes intracellular TFAM expression and activates its antioxidant pathway, thereby protecting mtDNA and alleviating oxidative stress and mitochondrial damage caused by MCAO in vivo and H2O2 stimulation in vitro. Lentivirus downregulates the expression of TFAM, and under its action, the antioxidant and mitochondrial protection effects of CAA are weakened. When TFAM was disrupted, the protective effect of CAA on mitochondria was inhibited. Compared to edaravone, a positive control, CAA exhibited similar therapeutic effects. These findings suggest that CAA alleviates CIRI through TFAM signaling pathways, offering potential therapeutic implications for ischemic stroke treatment.

Crohn’s disease is a chronic inflammatory bowel disease that is closely associated with genetic factors, immune dysregulation and microbial imbalance. Lesions involving the oral cavity and upper gastrointestinal tract constitute a common yet clinically overlooked manifestation of this disease. This article reviews the cellular and molecular mechanisms underlying disease onset and progression, and evaluates the diagnostic performance of various noninvasive and serum biomarkers. It also summarizes multimodal diagnostic approaches and corresponding therapeutic strategies based on current clinical practice. Currently, relevant clinical trials and standardized evaluation criteria remain lacking, largely because of the limited understanding of disease pathogenesis. Therefore, high-quality basic and translational research will be essential to deepen the understanding of this disease and facilitate the development of precision diagnostic and therapeutic strategies.

This study explored the protective effect and potential mechanism of carvacrol acetate (CAA) on the oxidation of chlorpyrifos (CPF). A model of oxidative stimulus damage was established in Sprague-Dawley rats by subcutaneous injection of the CPF poison. PC12 cells were used to construct an oxidative injury model using CPF, and the protective effects and mechanism of action of CAA against CPF-induced oxidative damage were explored in vitro. The key role of Nuclear factor erythroid-2-related factor 2 (Nrf2) in alleviating CPF-induced damage via CAA was further confirmed by administering Nrf2 inhibitors to PC12 cells. Administration of CAA significantly enhanced the locomotor ability of the rats, alleviated neuronal pathological alterations, and increased the number of Nissl bodies, while increasing autophagic bodies. In vitro, CAA promoted cell survival and augmented the mitochondrial membrane potential. It decreased both intra- and extracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), while markedly elevating mitochondrial DNA (mtDNA) copy number. Moreover, PC12 cells treated with Nrf2 inhibitors failed to exhibit any improvement in survival rate when treated with CAA after a toxic insult. Furthermore, ROS and MDA levels were not significantly reduced, SOD enzyme activity did not increase, and mitochondrial membrane potential and mtDNA copy number did not improve. Western blot analysis showed that the expression of Tfam, Beclin1, and LC3II/ LC3I proteins in the CAA group decreased significantly after Nrf2 inhibition. These findings suggest that CAA modulates mitochondrial function and autophagy by regulating the Nrf2 signalling pathway to mitigate the toxic damage. Finally, the effect of the autophagy inhibitor, 3-MA, on PC12 cells suggests that CAA promotes mitophagy by participating in the Nrf2 pathway, thereby preventing CPF-induced oxidative stress damage.

BACKGROUND:Chronic nonspecific low back pain (CNSLBP) is associated with thoracolumbar fascia (TLF) dysfunction. However, the structural effects of Gua Sha, a Traditional Chinese Medicine technique, remain unclear. This study aimed to explore the acute and short-term effects of Gua Sha therapy on TLF thickness, pain intensity, and related physiological parameters in patients with CNSLBP. METHODS:Thirty-two participants with CNSLBP were randomized to receive Gua Sha or hot pack therapy, a commonly used conservative treatment for low back pain, once a week for 4 weeks. The effects of the 2 treatments were compared. TLF thickness, pain, and related parameters were measured at baseline and immediately after the first and fourth interventions. A 2 (group) × 3 (time) repeated measures ANOVA was used for data analysis. RESULTS:With increasing intervention, both groups showed significant improvements in pain intensity and dysfunction (P < .001), significant reductions in tissue hardness and pressure pain threshold (P < .05), and significant increases in skin temperature and lumbar flexibility (P < .001). However, only the Gua Sha group significantly reduced TLF thickness immediately after the first intervention (MD = 0.388, 95% CI: 0.101-0.675; P = .01) and immediately after the fourth session (MD = 0.607, 95% CI: 0.199-1.015, P = .005). The heart rate variability-related indicators did not reach statistical significance (P > .05), but their trends were favorable. CONCLUSION:Gua Sha can effectively relieve pain, improve function, and regulate tissue mechanical properties in CNSLBP patients and its effects may be achieved through multiple pathways. Although the single and 4-session interventions were not significantly better than heat in improving fascial thickness, it performs better in pain and flexibility clinical outcomes, supporting its potential value as a complementary therapy. Future studies with larger samples and longer periods are needed to clarify its mechanism of action and optimize treatment options.

Skin, as the first line of defence of the human body, is exposed to dangers such as overheating substances, ultraviolet rays, and environmental pollutants, and the incidence of skin diseases is increasing annually. Oxidative stress plays a dominant role in most skin diseases. Abelmoschus manihot (L.) medic flower (TEA) is a traditional Chinese medicine widely used to treat injuries to the skin such as water and fire scalds. It has been reported that TEA has excellent antioxidant effects. In this study, we aimed to explore the antioxidant and mitochondrial protection effects of TEA in H2O2-mediated HaCaT cell damage. HaCaT cells were incubated with H2O2 to simulate oxidative stress in the skin. The effect of TEA on HaCaT cells was also evaluated. Cell morphology was observed via inverted microscopy, and cell viability was measured via the MTT reagent. The cells were stained with Hoechst 33,324 solution. Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and ATP detection kits were used to detect the corresponding indicators. The mitochondrial membrane potential was detected by JC-1. RT-PCR was used to detect mRNA and mtDNA expression. The expression of the target protein was detected by Western blotting and immunofluorescence. H2O2 triggered oxidative damage in HaCaT cells, which manifested as apoptosis, increased ROS and MDA contents, and decreased SOD activity. H2O2 activates the KEAP1/Nrf2/NQO1 signalling pathway, which decreases the expression of the intracellular KEAP1 protein and slightly increases the expression of the Nrf2 and NQO1 proteins, further causing mitochondrial oxidative stress, resulting in changes in the mitochondrial membrane potential, a reduction in the mtDNA copy number, and decreased expression of the PGC-1α and TFAM proteins. In addition the expression of mitochondrial respiratory chain genes and proteins decreased. TEA promoted the expression of Nrf2 in HaCaT cells, activated the downstream antioxidant response, and alleviated the oxidative stress and mitochondrial damage caused by H2O2. ML385 is an Nrf2 inhibitor, under which the antioxidant and mitochondrial protective effects of TEA are inhibited. When TFAM was knocked down, the protective effect of TEA on mitochondria was also inhibited. TEA protects HaCaT cells from H2O2-induced oxidative damage and mitochondrial oxidative damage through the KEAP1/Nrf2/NQO1/PGC-1α/TFAM pathway.

Many factors, including genetic vulnerability, barrier function, intestinal immune cells, and intestinal microbiota, may combine to affect the occurrence and progression of inflammatory bowel disease (IBD). Through targeting bile acid receptors (BARs), bile acids have been demonstrated to have a range of regulatory effects on intestinal immune responses in recent decades. As the basis of intestinal immunity, macrophages play an indispensable role in intestinal homeostasis. BARs connect the intestinal microbiota with immune cells, significantly impacting IBD. This review focuses on the role of bile acids in regulating the differentiation and function of intestinal macrophages in IBD.

Mitochondrial transcription factor A (TFAM) is a mitochondrial protein encoded by nuclear genes and transported from the cytoplasm to the mitochondria. TFAM is essential for the maintenance, expression, and delivery of mitochondrial DNA (mtDNA) and can regulate the replication and transcription of mtDNA. TFAM is associated with the formation of mtDNA nucleomimetic structures, mtDNA repair, and mtDNA stability. However, the mechanism by which TFAM protects mtDNA is still being studied. This review provides a summary of the protective mechanism of TFAM on mtDNA including the discrete regulatory effects of TFAM acetylation and phosphorylation on mtDNA, the regulation of Ca 2+ levels by TFAM to activate transcription in mitochondria, and the increased binding of TFAM to mtDNA damage hot spots. This review also discusses the association between TFAM and some neurodegenerative diseases.

Orexin (OX)A and OXB are a pair of neuropeptides secreted by orexin-producing neurons in the lateral hypothalamus. The orexin system can regulate many physiological processes through these two receptor pathways, such as feeding behavior, sleep/wake state, energy homeostasis, reward, and the coordination of emotion. Mammalian target of rapamycin (mTOR) can coordinate upstream signals with downstream effectors, thereby regulating fundamental cellular processes and also plays an essential role in the signaling network downstream of the orexin system. In turn, the orexin system can activate mTOR. Here, we review the association of the orexin system with the mTOR signaling pathway mainly by discussing that drugs in various diseases exert their effects on the orexin system, indirectly affecting the mTOR signaling pathway.

细胞程序性死亡(programmed cell death,PCD)是一种受基因调控的细胞死亡形式,在肿瘤等疾病的发生发展中有重要作用,根据其发生机制及形态特征可分为凋亡、坏死性凋亡、铁死亡、焦亡、自噬等.长链非编码RNA(long non-coding RNA,lncRNA)是转录物大于200个核苷酸的非编码RNA,通过直接或间接影响细胞内分子及蛋白的表达参与PCD的调控.本文就lncRNA参与调控PCD的相关文献进行总结,有望为lncRNA和PCD的进一步研究提供新的切入点,为相关临床疾病的诊疗及预防提供新的思路.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5 A, both FACS panels are identical and in Fig 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors' unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

The long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/β-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/β-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/β-catenin signaling could effectively abolish the activation of Wnt/β-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/β-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.

目的:制备漆黄素脂质体,并对其进行制剂学研究及体内外评价.方法:采用薄膜分散法制备漆黄素脂质体,以粒径为指标,通过单因素考察,制备不同磷脂与胆固醇总量、不同磷脂胆固醇比例及不同药脂比的漆黄素脂质体,确定漆黄素脂质体最优处方.采用激光散射粒径仪测定漆黄素脂质体的粒径、多分散系数、Zeta电位;采用超滤离心法测定漆黄素脂质体的包封率和载药量;对漆黄素脂质体的稳定性,在3种释放介质(pH 1.2盐酸、双蒸水和pH 7.4磷酸盐缓冲液)中的体外释放情况,细胞毒性以及药物代谢动力学等体内外参数进行评价.结果:采用最优处方(漆黄素22.2 mg、磷脂133.3 mg、胆固醇16.7 mg、胆酸钠110 mg、肉豆蔻酸异丙酯60 mg)制备的漆黄素脂质体平均粒径为(60.32±1.08)nm,多分散系数为0.198±0.011,包封率为(94.37±0.62)％,载药量为(4.500±0.021)％.透射电镜结果显示漆黄素脂质体外形圆整且分布均匀.制成脂质体后可提高漆黄素原料药的溶解度、体外释放率以及相对生物利用度;漆黄素脂质体在30 d内具有较好的稳定性.漆黄素脂质体对人肝癌HepG2细胞有明显的增殖抑制作用,且呈现剂量依赖关系.结论:漆黄素脂质体能显著提高难溶性药物漆黄素的溶解度和生物利用度.

目的:研究长链非编码RNA(long non-coding RNA,lncRNA)SPATA3-AS1在胃癌患者癌组织和血浆中的表达及临床意义,并进一步探讨其对胃癌细胞株的影响及其潜在机制.方法:采用实时荧光定量PCR(qRT-PCR)检测80例胃癌及癌旁组织、29例胃癌患者和29例健康者血浆中SPATA3-AS1的表达水平;对胃癌患者SPATA3-AS1表达与其临床病理特征行统计学分析.敲减SPATA3-AS1,分别转染胃癌AGS、HGC-27细胞,采用细胞增殖、克隆形成、Transwell实验及流式细胞术分别检测细胞增殖、迁移、侵袭和凋亡;采用qRT-PCR检测肿瘤相关基因mRNA的表达水平.结果:SPATA3-AS1在胃癌组织中呈高表达,其表达与淋巴结转移、肿瘤TNM分期、肿瘤浸润深度及肿瘤预后相关;胃癌患者血浆中SPATA3-AS1也呈高表达,其表达与淋巴结转移、肿瘤直径、肿瘤TNM分期呈正相关.血浆中SPATA3-AS1表达水平诊断胃癌ROC曲线下面积为0.788.敲减SPATA3-AS1后,胃癌AGS、HGC-27细胞增殖及移动活力减弱,细胞凋亡能力增强.同时N-钙黏蛋白、Twist1、Snail mRNA表达下调而E-钙黏蛋白mRNA表达上调.结论:SPATA3-AS1在胃癌患者癌组织及血浆中呈高表达并与其预后相关;敲减SPATA3-AS1后胃癌细胞增殖、迁移及侵袭等能力均受到抑制,细胞凋亡增强,可能与对上皮间质转化过程的调控有关.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5A, both FACS panels are identical and in Fig. 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and Fig. 5E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors’ unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

The objective of this study was to evaluate the effects of rumen-protected betaine supplementation on performance of postpartum dairy cows and immunity of newborn calves. Twenty-four multiparous Holstein dairy cows were randomly divided into the control (CON, n = 12) and rumen-protected betaine (BET, n = 12) groups after blocking by parity and milk yield during the previous lactation cycle. The cows were fed a basal total mixed ration diet without BET (CON) or with BET at 20 g/d per cow (BET) from four weeks before expected calving to six weeks postpartum. The results showed that betaine supplementation had no effect on dry matter intake and milk yield of the cows. The BET cows tended to increase feed efficiency (energy-corrected milk/dry matter intake) and body weight loss postpartum compared to the CON cows. The plasma β-hydroxybutyrate concentrations of the BET cows were greater at d seven after calving than those of the CON cows. Moreover, compared to the CON calves, the BET calves had greater plasma total protein and globulin concentrations. The plasma glucose concentrations of the BET calves tended to decrease relative to CON cows. In conclusion, rumen-protected betaine supplementation from four weeks before expected calving tended to increase fat mobilization of postpartum dairy cows, and might improve the immunity of newborn calves.

Background Mastitis is the most frequent diseases for transition cows. Identification of potential biomarkers for diagnosis of mastitis is important for its prevention. Thus, this study was conducted to investigate blood variables related to lipid metabolism, oxidative stress and inflammation, and serum variables that are related to health in postpartum cows. Results Seventy-six healthy Holstein dairy cows at week 4 before calving were selected to collect blood samples from weeks − 4 to 4 weekly relative to calving, respectively. Milk yield and composition were recorded weekly. According to the cut-off of somatic cell counts (SCC) for diagnosis of mastitis, 33 cows with SCC ≥ 500,000 cells ml − 1 , 20 cows with 200,000 cells ≤ SCC < 500,000 cells ml − 1 , and 23 cows with SCC < 200,000 cells ml − 1 were defined as high, middle, and low SCC, respectively. Serum concentrations of β-hydroxybutyrate were higher ( P < 0.01) during all weeks, and non-esterified fatty acids were higher in high SCC than in low SCC cows from weeks − 3 to 2 relative to calving. Higher serum concentrations of superoxide dismutase ( P < 0.01) and lower malondialdehyde levels ( P < 0.01) in low SCC than in high SCC cows indicate that the latter suffered from oxidative stress. The difference analysis of the three groups suggested that none of the above-mentioned variables can be used as potential prognostic candidates. On the other hand, high SCC cows exhibited higher blood neutrophil to lymphocyte ratio (NLR, P < 0.01) and platelet to lymphocyte ratio (PLR, P < 0.01) than low SCC cows, with a higher NLR ( P < 0.01) in middle SCC than in low SCC cows. The high SCC cows had lower levels of anti-inflammatory factors including IL-10 ( P = 0.05), but higher levels of proinflammatory factors such as IL-6 ( P < 0.01), TNF-α ( P < 0.05), and PSGL-1 ( P < 0.01) than low SCC cows. Conclusions The significantly different NLR and PLR pre-partum between the middle and low SCC cows suggest their prognostic potential for postpartum mastitis risk.

Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease that mainly affects the spinal cord and optic nerve, causing blindness and paralysis in some individuals. Moreover, NMO may cause secondary complement-dependent cytotoxicity (CDC), leading to oligodendrocyte and neuronal damage. In this study, a rodent NMO model, showing typical NMO pathogenesis, was induced with NMO-IgG from patient serum and human complement. We then tested whether the combination of C16, an αvβ3 integrin-binding peptide, and angiopoietin-1 (Ang1), a member of the endothelial growth factor family, could alleviate NMO in the model. Our results demonstrated that this combination therapy significantly decreased disease severity, inflammatory cell infiltration, secondary demyelination, and axonal loss, thus reducing neural death. In conclusion, our study suggests a possible treatment that can relieve progressive blindness and paralysis in an animal model of NMO through improvement of the inflammatory milieu.