Novel positioning guiders accurately assist in situ acetabular reconstruction for patients undergoing pelvic bone tumor resection.

PURPOSE: Acetabular reconstruction in situ after extensive pelvic resection is technically challenging. The aim of this study was to investigate the feasibility of positioning guiders for acetabular reconstruction following pelvic tumor resection and the clinical benefit brought by the approach. METHODS: The study included patients who underwent acetabular reconstruction following periacetabular tumor resection using a modular hemipelvic prosthesis. In the guider-assisted group (n = 14), guiders were designed and applied to assist acetabular reconstruction. In the traditional operation group (n = 18), the patients underwent the same surgery but without the guiders. The displacement of the hip rotation center before and after surgery was calculated. The complications and the Musculoskeletal Tumor Society-93 scores were documented. RESULTS: The overall displacement of the hip rotation center was significantly reduced in the guider-assisted group compared with the traditional operation group (13.83 ± 4.06 vs. 22.95 ± 9.18 mm in P = 0.000, 95%CI 3.90-12.96), especially in the anteroposterior axis (3.77 ± 3.03 versus 13.51 ± 9.43 mm in P = 0.000, 95%CI 3.45-13.09). Guider-assisted acetabular reconstruction reduced the risk of prosthesis dislocation compared with the traditional operation (dislocation risks: 1/14, 7.1% vs. 4/18, 22.2%). CONCLUSION: Positioning guiders can effectively and conveniently help place the modular hemipelvic prosthesis at the native position, which might potentially reduce the risk of prosthesis dislocation. LEVEL OF EVIDENCE: Therapeutic level III.

Effects of comprehensive nursing intervention on pressure ulcer after traumatic brain injury surgery: A meta-analysis.

Pressure ulcers (PUs) are a common complication in postoperative patients with traumatic brain injury, and this study used a meta-analysis to assess the effects of comprehensive nursing applied in PUs intervention in postoperative patients with traumatic brain injury. A computerised systematic search of the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (CBM), VIP and Wanfang databases was performed to collect publicly available articles on randomised controlled trials (RCTs) on the effects of comprehensive nursing interventions in postoperative patients with traumatic brain injury published up to August 2023. Two researchers independently completed the search and screening of the literature, extraction of data and quality assessment of the included literature based on the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Twenty-eight articles were finally included, for a cumulative count of 2641 patients, of which 1324 were in the intervention group and 1317 in the control group. The results of the meta-analysis showed that, compared with conventional nursing, comprehensive nursing intervention helped to reduce the incidence of PUs in postoperative patients with traumatic brain injury (5.14% vs. 19.67%, odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.16-0.29, p < 0.00001) and reduced the incidence of postoperative complications (7.87% vs. 25.84%, OR: 0.22, 95% CI: 0.11-0.43, p < 0.0001), while increasing patient satisfaction (96.67% vs. 75.33%, OR: 9.5, 95% CI: 3.63-24.88, p < 0.00001). This study concludes that a comprehensive nursing intervention applied to postoperative patients with traumatic brain injury can significantly reduce the incidence of PUs and postoperative complications as well as improve nursing satisfaction, and it is recommended for clinical promotion. However, due to the limitations of the studies' number and quality, more high-quality, large-sample RCTs are needed to further validate the conclusions of this study.

Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time-scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.

Conversion from Spanning External Fixation to Open Reduction Internal Fixation Contributes to Healing of Soft Tissues and Fractures in Open Distal Humeral Fractures.

BACKGROUND Open distal humeral fractures (DHFs) often lead to loss of elbow function, thereby seriously affecting patient quality of life. The aim of this study was to evaluate the treatment outcomes of 2 surgical techniques to determine the better method for repairing open DHFs. Both groups were treated with immediate debridement first, and then group I had only internal fixation (IF), while group II underwent initial external fixation (EF) followed by IF surgery. MATERIAL AND METHODS This retrospective study included 32 patients who had open DHFs between 2013 and 2018. Twelve patients underwent thorough debridement and temporary EF treatment and converted to IF as the ultimate treatment. Twenty patients were treated with immediate open reduction and internal fixation (ORIF). Data of final treatment outcomes were analyzed at the latest follow-up. A comparative analysis of radiological results, function observations, and complications was performed for the 2 surgical groups. RESULTS All DHFs and osteotomized olecranon united after a mean of 5.2±1.21 months. No significant differences were observed in other preoperative demographic data between the 2 groups. Moreover, there was no significant difference in postoperative complications, elbow range of motion, or fracture healing time between the 2 groups. CONCLUSIONS The evidence provided by our study highlights the efficacy of definitive IF in treating open DHFs, which is recommended whenever possible. Furthermore, the combination of EF and ORIF, according to the type of soft tissue damage, may be a promising treatment option with a low revision rate for patients with open DHFs.

FoxO1a mediated cadmium-induced annulus fibrosus cells apoptosis contributes to intervertebral disc degeneration in smoking.

Cadmium (Cd), a type of heavy metal that accumulates in the body because of smoking, mediates the toxic effect of smoking in many diseases, such as cardiovascular disease, osteoarthritis, and osteoporosis. However, the toxic effect of Cd on intervertebral disc tissues have not been reported. In the current study, we demonstrated that Cd induced the apoptosis of annulus fibrosus (AF) cells, which contributed to intervertebral disc degeneration (IVDD). Specifically, Cd induced the nuclear translocation of FoxO1a, which drives AF cells apoptosis through mitochondrial-related pathway. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signal pathway is also involved in this process. The combined use of LY29002, an inhibitor of PI3K, and small interfering RNA-targeting FoxO1a confirmed the relationship between the PI3K/AKT signal pathway and FoxO1a. In summary, present research explores the mechanism behind the contribution of smoking to IVDD and finds a new feasible target for preventing IVDD in smoking.

Compression stress induces nucleus pulposus cell autophagy by inhibition of the PI3K/AKT/mTOR pathway and activation of the JNK pathway.

Purpose: Reactive oxygen species (ROS) are related to compression stress-induced nucleus pulposus (NP) cell autophagy, but the specific mechanism is unknown in compression stress-induced intervertebral disc degeneration (IVDD). Here, we discuss the specific molecular mechanism and explore whether ROS scavengers could be employed as specific drugs to inhibit compression stress-induced IVDD.Methods: Rat NP cells were exposed to 1.0 MPa compression and pretreatment with the ROS scavenger N-acetylcysteine (NAC) or the JNK-selective inhibitor SP600125 not. Intracellular ROS production was monitored by confocal microscopy. Autophagy was detected by observing the NP cell ultrastructural features using TEM and examining autophagic vacuoles by flow cytometry. The levels of autophagy-associated molecules, the JNK pathway and the PI3K/AKT/mTOR pathway were analyzed by western blotting.Results: Compression-mediated autophagy in rat NP cells was implicated in ROS generation. The ROS scavenger NAC could protect compression-induced NP cell injures by inhibiting ROS production. And SP600125, a JNK inhibitor, attenuated compression-induced NP cell autophagy. Additionally, this is the first report showing that compression induces autophagy in rat NP cells by impeding the compression-induced ROS dependent PI3K/AKT/mTOR pathway and the ROS independent activation of JNK pathway. And the involvement of JNK pathway was in different mechanism of action that when inhibited leaded to increased cell death, increased generation of ROS but decreased autophagy.Conclusions: These results show a new regulatory mechanism involving ROS-mediated autophagy in rat NP cells, which may provide ideas for drug development to improve compression stress-induced IVDD and help avoid eventual surgical treatment of IVD herniation.

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation.

Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.

Compression-induced senescence of nucleus pulposus cells by promoting mitophagy activation via the PINK1/PARKIN pathway.

The current research aimed to explore the possible relationship between PINK1/PARKIN-mediated mitophagy and the compression-induced senescence of nucleus pulposus cells (NPCs). Therefore, the stages of senescence in NPCs were measured under compression lasting 0, 24 and 48 hours. The mitophagy-related markers, autophagosomes and mitochondrial membrane potential were tested to determine the levels of PINK1/PARKIN-mediated mitophagy under compression. The PINK1 and PARKIN levels were also measured by immunohistochemistry of human and rat intervertebral disc (IVD) tissues taken at different degenerative stages. A specific mitophagy inhibitor, cyclosporine A (CSA) and a constructed PINK1-shRNA were used to explore the relationship between mitophagy and senescence by down-regulating the PINK1/PARKIN-mediated mitophagy levels. Our results indicated that compression significantly enhanced the senescence of NPCs in a time-dependent manner. Also, PINK1/PARKIN-mediated mitophagy was found to be activated by the extended duration of compression on NPCs as well as the increased degenerative stages of IVD tissues. After inhibition of PINK1/PARKIN-mediated mitophagy by CSA and PINK1-shRNA, the senescence of NPCs induced by compression was strongly rescued. Hence, the excessive degradation of mitochondria in NPCs by mitophagy under continuous compression may accelerate the senescence of NPCs. Regulating PINK1/PARKIN-mediated mitophagy might be a potential therapeutic treatment for IVD degeneration.

TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy.

To investigate whether TP53-induced glycolysis and apoptosis regulator (TIGAR) participates in compression-induced intervertebral disc (IVD) degeneration, and to determine the regulatory effect of TIGAR on nucleus pulposus (NP) cell autophagy and apoptosis following compression-induced injuries. IVD tissues were collected from human patients undergoing surgery (n = 20) and skeletally mature Sprague-Dawley rats (n = 15). Initially, the effect of compression on the expression of TIGAR was evaluated with in vivo and in vitro models. In addition, TIGAR was silenced to investigate the regulatory effect of TIGAR on compression-induced intracellular reactive oxygen species (ROS) levels, autophagy, and apoptosis in rat NP cells. Furthermore, the P53 inhibitor pifithrin-α (PFTα) and SP1 inhibitor mithramycin A were employed to detect expression level changes of TIGAR and autophagy-associated target molecules. TIGAR expression of NP cells increased gradually in human degenerative IVDs and in rat NP cells under compression both in vivo and in vitro. TIGAR knockdown enhanced compression-induced intracellular ROS generation and the NADPH/NADP+ and GSH/GSSG ratios. Moreover, TIGAR knockdown amplified the compression-induced caspase-3 activation and the apoptosis rate of rat NP cells. Likewise, knockdown of TIGAR significantly accelerated LC3B expression and autophagosome formation in rat NP cells during compression-induced injuries. The results also established that mithramycin A could inhibit TIGAR expression and autophagy levels in NP cells under compression conditions, while PFTα had no similar effect. Our data demonstrated that TIGAR acted as an important endogenous negative regulator of ROS levels, which might inhibit compression-induced apoptosis and autophagy through SP1-dependent mechanisms.

Moderate activation of Wnt/ß-catenin signaling promotes the survival of rat nucleus pulposus cells via regulating apoptosis, autophagy, and senescence.

This study aimed to investigate the specific role of Wnt/ß-catenin signaling in compression-induced apoptosis, autophagy, and senescence in rat nucleus pulposus (NP) cells. Initially, the cells underwent various periods of exposure to 1.0 MPa compression. Wnt/ß-catenin signaling associated molecules were assessed in detail, and then 0, 24 and 48 hours exposure periods were selected. The cells were then divided into control, Wnt/ß-catenin inhibitor (IWP-2), Wnt/ß-catenin activator (LiCl), and ß-catenin overexpression groups. After 0, 24, and 48 hours of compression, apoptosis, autophagy, and senescence were evaluated by Western blot analysis and real-time polymerase chain reaction and were visually observed by Hoechst33258, monodansylcadaverine, and SA-ß-gal stainings, respectively. Additionally, the regulatory effect of Wnt/ß-catenin signaling on cell morphology, viability, cell cycle, death ratio, and ultrastructure was detected to thoroughly evaluate the survival capacity of NP cells. The results established that compression elicited a time-dependent activation of Wnt/ß-catenin signaling. The IWP-2 treatment decreased cell survival rate, which corresponded to downregulation of autophagy as well as increases in apoptosis and senescence. LiCl treatment enabled more efficient of cell survival accompanied by increased autophagy and downregulated apoptosis and senescence; however, in contrast to LiCl, overexpression of ß-catenin aggravated compression-induced NP cells death. In conclusion, moderate activation of Wnt/ß-catenin signaling enables more efficient of NP cells survival via downregulation of apoptosis, senescence, and upregulation of autophagy, and overactivation of Wnt/ß-catenin signaling achieved the opposite effect. Treatment strategies that aim to regulate Wnt/ß-catenin signaling might be a novel target for improving compression-induced NP cells death and potential treatment of intervertebral disc degeneration.

MiR-20a, a novel promising biomarker to predict prognosis in human cancer: a meta-analysis.

BACKGROUND: Recently, microRNA-20a (miR-20a) has been reported to influence the clinical features and may have prognostic value in human cancers. The present meta-analysis assessed the prognostic role of miR-20a in various carcinomas. METHODS: Literature searches of seven electronic databases were performed for eligible articles of the prognostic role of miR-20a in human cancers. Hazard ratios (HR) for overall survival (OS), disease free survival (DFS), progression-free survival (PFS) as well as their 95% confidence intervals (95%CIs) were used to assess the influence of miR-20a expression on patient prognosis. Odds ratio (OR) and 95%CIs were applied to evaluate the correlation between miR-20a expression and clinicopathological characteristics. RESULTS: Based on the OS analyzed by log rank tests, there was a significant association between miR-20a levels and OS by fixed effects model. By subgroup analyses, the significance was also observed in the studies of specimen derived from blood and gastrointestinal cancer group. The independent prognostic role of miR-20a expression for the OS was observed significantly by fixed effects model. In addition, we observed significant association between miR-20a expression levels and DFS of log rank tests, DFS of cox regression. Significant relation of gender/differentiation and the expression level of miR-20a was identified. CONCLUSIONS: Base on the findings, the elevated miR-20a expression level is related to poor prognosis of gastrointestinal cancer patients. As for other types of carcinomas, the results are still not stable and more studies are required to further identify miR-20a prognostic values. In addition, miR-20a expression level is relatively higher in women than that in men, and increased miR-20a expression level is linked to poor tumor differentiation.

Association of COL9A3 trp3 polymorphism with intervertebral disk degeneration: a meta-analysis.

BACKGROUND: Intervertebral disk degeneration (IDD) is a common musculoskeletal disease associated with genetic factors. COL9A3 gene encodes the α3 (IX) chain of type IX collagen that is part of the interior structure of the disc. Mutations in COL9A3 gene sequence, leading to an Arg103Trp substitution in its 3 chain (the Trp3 allele at rs61734651 site), respectively, have been found to be connected with IDD occurrence in several studies. However, those studies have showed conflict results. Thus, a meta-analysis has been performed to assess the associations between the COL9A3 trp3 polymorphism and IDD. METHODS: Data were gathered from the following four electronic databases: PubMed, Web of Science (WOS), Embase and Cochrane library up to January 01, 2018. The pooled odds ratio (polled ORs) and 95% confidence interval (CI) were calculated to evaluate the strength of relationship between the COL9A3 trp3 polymorphism and IDD. RESULTS: Eleven eligible studies with 1631 cases of IDD and 1366 controls were included in this meta-analysis. The results indicated that the COL9A3 trp3 polymorphism was not associated with IDD (trp3 positive versus trp3 negative: OR = 1.31, 95%CI = 0.78-2.21, P = 0.309). Furthermore, the Egger's test and the Begg funnel plot did not show any evidence of publication bias. CONCLUSIONS: Our results suggest that the COL9A3 trp3 polymorphism might not be associated with IDD. Nor did we find any relationship in subgroup analyses stratified by gender and ethnicity. Future researches with larger samples are required to verify this outcome.

Association between Fas/FasL gene polymorphism and musculoskeletal degenerative diseases: a meta-analysis.

BACKGROUND: It was reported that Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) gene polymorphism might be related to the risk of musculoskeletal degenerative diseases (MSDD), such as osteoarthritis (OA), intervertebral disc degeneration (IVDD) and rheumatoid arthritis (RA). However, data from different studies was inconsistent. Here we aim to elaborately summarize and explore the association between the Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) and MSDD. METHODS: Literatures were selected from PubMed, Web of Science, Embase, Scopus and Medline in English and VIP, SinoMed, Wanfang and the China National Knowledge Infrastructure (CNKI) in Chinese up to August 21, 2017. All the researches included are case-control studies about human. We calculated the pooled odds ratios (ORs) with 95% confidence intervals (95% CI) to evaluate the strengths of the associations of Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) polymorphisms with MSDD risk. RESULTS: Eleven eligible studies for rs1800682 with 1930 cases and 1720 controls, 6 eligible studies for rs2234767 with 1794 cases and 1909 controls, 3 eligible studies for rs5030772 with 367 cases and 313 controls and 8 eligible studies for rs763110 with 2010 cases and 2105 controls were included in this analysis. The results showed that the G allele of Fas (rs1800682) is associated with an increased risk of IVDD in homozygote and recessive models. The G allele of Fas (rs2234767) is linked to a decreased risk of RA but an enhanced risk of OA in allele and recessive models. In addition, the T allele of FasL (rs763110) is correlated with a reduced risk of IVDD in all of models. However, no relationship was found between FasL (rs5030772) and these three types of MSDD in any models. CONCLUSIONS: Fas (rs1800682) and FasL (rs763110) polymorphism were associated with the risk of IVDD and Fas (rs2234767) was correlated to the susceptibility of OA and RA. Fas (rs1800682) and Fas (rs2234767) are more likely to be associated with MSDD for Chinese people. FasL (rs763110) is related to the progression of MSDD for both Caucasoid and Chinese race groups. But FasL (rs5030772) might not be associated with any types of MSDD or any race groups statistically.

Association of TNF-α-308(G/A) and -238(G/A) polymorphisms with non-traumatic osteonecrosis of the femoral head risks: a meta-analysis.

PURPOSE: The association between TNF-α-308(G/A) and -238(G/A) polymorphisms and the susceptibility of non-traumatic osteonecrosis of the femoral head (NONFH) was investigated in many studies with conflicting results. We aimed to conduct a meta-analysis to evaluate the relationship between them comprehensively. METHODS: Relevant literatures published in PubMed, Web of Science, Embase, Cochrane library databases, China National Knowledge Infrastructure (CNKI), WANFANG Data, and China Science and Technology Journal Database (CSTJ) updated to January 30, 2018, were reviewed by two investigators independently. Odds ratios (ORs) and its 95% confidence intervals (95% CIs) were calculated by a fixed-effect model based on the indistinctive heterogeneity. RESULTS: For TNF-α-308(G/A) polymorphism, we recruited five studies including 432 NONFH patients and 760 controls and a statistically significant association was identified in Asians in four modes consisting of alleles mode (OR = 0.648, 95% CI 0.475-0.885), homozygote mode (OR = 0.330, 95% CI 0.136-0.802), dominant mode (OR = 0.344, 95% CI 0.143-0.827), and recessive mode (OR = 0.674, 95% CI 0.468-0.971), but no significant association was observed in Caucasians. For TNF-α-238(G/A) polymorphism, three eligible studies including 275 cases and 610 controls were evaluated and there was a significant association in alleles mode (OR = 0.270, 95% CI 0.4148-0.490) as well as recessive mode (OR = 0.254, 95% CI 0.138-0.468). CONCLUSION: This meta-analysis shows that TNF-α-308(G/A) and -238(G/A) polymorphisms are associated with the susceptibility of NONFH, while the significant association for 308(G/A) is mainly observed in Asians.

Effect of S100A6 over-expression on ß-catenin in endometriosis.

AIM: S100A6 is over-expressed in several human tumors, including pancreatic carcinoma, malignant fibrous histiocytoma, breast, colon, and gastric carcinoma, but little is known about the role of S100A6 in endometriosis. The aim of the present study was to investigate the effect of S100A6 over-expression on ß-catenin in endometrial stromal cells. METHODS: Endometrial stromal cells were transfected with an hS100A6-expressing recombinant lentivirus construct. The expression of ß-catenin was assessed using western blot and reverse transcription-polymerase chain reaction. RESULTS: S100A6 over-expression promoted ß-catenin expression at the RNA and protein levels, in endometrial stromal cells. CONCLUSIONS: S100A6 induces expression of ß-catenin in endometrial stromal cells.

USP18 Curbs the Progression of Metabolic Hypertension by Suppressing JAK/STAT Pathway.

Hypertension is a pathological state of the metabolic syndrome that increases the risk of cardiovascular disease. Managing hypertension is challenging, and we aimed to identify the pathogenic factors and discern therapeutic targets for metabolic hypertension (MHR). An MHR rat model was established with the combined treatment of a high-sugar, high-fat diet and ethanol. Histopathological observations were performed using hematoxylin-eosin and Sirius Red staining. Transcriptome sequencing was performed to screen differentially expressed genes. The role of ubiquitin-specific protease 18 (USP18) in the proliferation, apoptosis, and oxidative stress of HUVECs was explored using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. Moreover, USP18 downstream signaling pathways in MHR were screened, and the effects of USP18 on these signaling pathways were investigated by western blotting. In the MHR model, total cholesterol and low-density lipoprotein levels increased, while high-density lipoprotein levels decreased. Moreover, high vessel thickness and percentage of collagen were noted along with increased malondialdehyde, decreased superoxide dismutase and catalase levels. The staining results showed that the MHR model exhibited an irregular aortic intima and disordered smooth muscle cells. There were 78 differentially expressed genes in the MHR model, and seven hub genes, including USP18, were identified. USP18 overexpression facilitated proliferation and reduced apoptosis and oxidative stress in HUVECs treated with Ang in vitro. In addition, the JAK/STAT pathway was identified as a USP18 downstream signaling pathway, and USP18 overexpression inhibited the expression of JAK/STAT pathway-related proteins. Conclusively, USP18 restrained MHR progression by promoting cell proliferation, reversing apoptosis and oxidative stress, and suppressing the JAK/STAT pathway.

Sensitive sandwich-type electrochemical immunosensing of p53 protein based on Ti3C2Tx MXene nanoribbons and ferrocene/gold.

Since the p53 protein is an important promising biomarker of lung tumor and colorectal tumor, it is very essential to design a highly effective mean to monitor the degree of p53 for the early clinical analysis/therapy of the related tumors. In this work, a sandwich-type electrochemical immunosensing (SES) platform is proposed for the first time to detect p53 via synthesizing Ti3C2Tx MXene nanoribbons (Ti3C2Tx Nb) and ferrocene/gold nanoparticles (Fc/Au) respectively as the sensing substrate and signal-amplifier. The superior electrical property and large surface area of Ti3C2Tx Nb are beneficial to assemble the initial p53-antibodies (Ab1), while the synthesized Fc/Au is devoted to assemble the secondary p53 antibodies (Ab2) and gives a magnified signal. By adopting the Fc molecules as the probes, the experiments reveal the response current of Fc resulted from the SES structure increases along with the p53 increase from 1.0 to 200.0 pg mL-1. A considerable low detection limit (1.0 pg mL-1) is achieved after optimizing several key conditions, it is thus confirmed the as-proposed SES mean exhibits significant application in the detection of p53 protein and other targets.

The effects of semaphorin 3A in bone and cartilage metabolism: fundamental mechanism and clinical potential.

Semaphorin 3A (Sema3A) is a neuroinformatic protein molecule with widespread expression across various tissues and organs. Recent investigations have unveiled its pivotal role in the skeletal system, primarily through its binding interactions with two co-receptors, neuropilin-1 (Nrp-1) and members of the plexin family. Prior research has confirmed the expression of Sema3A and its receptors in both osteocytes and chondrocytes. Beyond its expression patterns, Sema3A plays a multifaceted role in regulating bone and cartilage metabolism via employing diverse signaling pathways. Additionally, it engages in collaborative interactions with the immune and nervous systems, contributing to the pathophysiological processes underlying a spectrum of bone and joint diseases. In this paper, we undertake a comprehensive review of recent research developments in this field. Our objective is to deepen the understanding of Sema3A within the context of skeletal physiology and pathology. Furthermore, we aim to furnish a valuable reference for potential therapeutic interventions in the realm of bone and joint diseases.