Utilizing a structure-based virtual screening approach to discover potential LSD1 inhibitors.

BACKGROUND: Lysine-specific demethylase 1 (LSD1) is highly expressed in a variety of malignant tumors, rendering it a crucial epigenetic target for anti-tumor therapy. Therefore, the inhibition of LSD1 activity has emerged as a promising innovative therapeutic approach for targeted cancer treatment. METHODS: In our study, we employed innovative structure-based drug design methods to meticulously select compounds from the ZINC15 database. Utilizing virtual docking, we evaluated docking scores and binding modes to identify potential inhibitors. To further validate our findings, we harnessed molecular dynamic simulations and conducted meticulous biochemical experiments to deeply analyze the binding interactions between the protein and compounds. RESULTS: Our results showcased that ZINC10039815 exhibits an exquisite binding mode with LSD1, fitting perfectly into the active pocket and forming robust interactions with multiple critical residues of the protein. CONCLUSIONS: With its significant inhibitory effect on LSD1 activity, ZINC10039815 emerges as a highly promising candidate for the development of novel LSD1 inhibitors.

Direct Anterior Approach Total Hip Arthroplasty for Femoral Neck Fractures in the Lateral Position.

Objective: To compare the clinical efficacy of artificial total hip arthroplasty(THA) for femoral neck fracture between direct anterior approach(DAA) in lateral position and posterior lateral approach(PLA). Methods: Comparison of 200 cases of patients who underwent THA collected between September 2019 and August 2021 was done. Incision length, intraoperative bleeding, operative time, difference in postoperative haemoglobin from preoperative levels, length of hospital stay, postoperative time to get off the floor, visual analogue score (VAS) for pain, preoperative and postoperative Harris scores for the hip, and measurements of the acetabular abduction angle and anterior acetabular tilt angle at 6 months postoperatively were collected, and all the cases were followed up for at least 2 years. Results: Compared with the PLA group, the DAA group had a shorter incision length, less intraoperative blood loss, less postoperative haemoglobin reduction compared with the preoperative period, a shorter hospital stay and an earlier first time to get off the floor after surgery, however, the comparison of operative times was not statistically significant; Patients in the DAA group had a lower VAS in the early postoperative period compared to PLA; Patients in the DAA group had higher hip Harris scores at 6 weeks and 6 months postoperatively; There was no significant difference in acetabular abduction angle and acetabular anterior tilt angle between the two groups at 6 months postoperatively. Conclusion: Compared to PLA, DAA in THA is minimally invasive, has less pain, less bleeding, earlier time out of bed, shorter hospital stay, better early hip function, faster rehabilitation, and better joint stability.

Cadmium-induced annulus fibrosus cell senescence contributes to intervertebral disc degeneration via the JNK/p53 signaling pathway.

Objectives: Investigating the impact of cadmium (Cd) on annulus fibrosus (AF) cells and its potential mechanism was the purpose of the current study. Materials and Methods: Cd was cultivated in different concentrations (0, 1, 5, 10, and 20 µM) on AF cells and the potential effects of the metal were assessed. Using the CCK-8 method, cell viability and proliferation were identified. Using transcriptome analysis, the annulus fibrosus cells were sequenced both with and without cadmium chloride. The EdU method was used to determine the rate of cell proliferation; senescence-associated ß-galactosidase (SA-ß-Gal) staining was used to determine the number of positive cells; and western blot, RT-PCR, and immunofluorescence were used to determine the protein and mRNA expression of senescence-associated proteins (p16, p21, and p53) and c-Jun N-terminal kinase (JNK). Results: According to the findings, Cd has the ability to increase the production of senescence-associated genes (p16 and p21) and senescence-associated secreted phenotype (SASP), which includes IL-1ß and IL-6. Through the JNK/p53 signal pathway, Cd exposure simultaneously accelerated AF cell senescence and promoted SASP. Following JNK inhibitor (SP600125) treatment, the expression of p53, JNK, and senescence-associated indices were all down-regulated. Conclusion: By activating the JNK/p53 signaling pathway, Cd can induce oxidative stress damage and AF cell senescence. These findings could provide a new approach for treating and preventing intervertebral disc degeneration (IVDD) caused by Cd exposure.

Suture Bridge Technique with 5-Ethibond: A Promising Approach for Infrapatellar Pole Fracture Treatment.

Purpose: Infrapatellar pole fractures are challenging injuries that require appropriate treatment to ensure optimal functional outcomes. This study aimed to introduce the application of the Suture Bridge technique using the 5-Ethibond for the treatment of infrapatellar patella fracture. Methods: Five cases of infrapatellar pole fracture that were treated at our institution between February 2020 and September 2021. The patients included one male and four females, with an average age of 66 years (range: 60-77 years). All patients were treated with the Suture Bridge technique using the 5-Ethibond to preserve the infrapatellar pole. Results: The average operative time was 64 min (range: 50-80 min). The average blood loss during surgery was 51 mL (range: 40-60 mL). All cases demonstrated fracture healing at an average of 10 weeks (range 8-12) after surgery. The patients were followed up for an average period of 14.8 months (8-22). No wound infection or second displacement of fracture fragment was found. Full range of motion was restored in all patients within 12-14 weeks after surgery. None of the patients complained of anterior knee pain. Conclusions: Based on the findings of the study, it appears that the Suture Bridge technique using 5-Ethibond is a promising and viable option for the treatment of infrapatellar pole fractures.

Human umbilical cord mesenchymal stem cells overexpressing RUNX1 promote tendon-bone healing by inhibiting osteolysis, enhancing osteogenesis and promoting angiogenesis.

BACKGROUND: Rotator cuff injury (RCI) is a common shoulder injury, which is difficult to be completely repaired by surgery. Hence, new strategies are needed to promote the healing of tendon-bone. OBJECTIVE: We aimed to investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing RUNX1 on the tendon-bone healing after RCI, and to further explore its mechanism. METHODS: Lentiviral vector was used to mediate the overexpression of RUNX1. RUNX1-overexpressed UCB-MSCs (referred to as MSC-RUNX1) were co-cultured with osteoclasts, and TRAP staining was performed to observe the formation of osteoclasts. Then MSC-RUNX1 was cultured in osteogenic differentiation medium, Alizarin red staining was conducted to detect osteogenic differentiation. The expression of markers of osteogenesis and osteoclast was detected by RT-qPCR. EA. hy926 cells were co-cultured with MSC-RUNX1. Transwell assay was used to detect the migration, and the expression of angiogenesis related-genes VEGF and TGF-ß was detected by RT-qPCR. The rat rotator cuff reconstruction model was established and MSCs were injected at the tendon-bone junction. Biomechanical test and micro-CT scanning were performed, and HE, Masson and Alcian Blue staining were used for histological evaluation of tendon-bone healing. TUNEL and PCNA immunofluorescence (IF) staining were performed to evaluate apoptosis and proliferation at the tendon-bone healing site. The levels of TNF-α, IL-6 and IL-8 in serum were detected by ELISA. The expression of CD31 and Endomucin that related to angiogenesis was detected by IF. Safranin O-fast and TRAP/CD40L immunohistochemical staining were used to assess the levels of osteoclasts and osteoblasts at the tendon-bone healing site. RESULTS: hUC-MSCs overexpressing RUNX1 inhibited osteoclast formation and promoted osteogenic differentiation. MSC-RUNX1 could promote the migration and tube formation of EA. hy926 cells, and up-regulate the levels of VEGF and TGF-ß. Model mice treated with MSC-RUNX1 partially restored the biomechanical indexes. Treatment of MSC-RUNX1 obviously increased the bone density, accompanied by the formation of new bone. In vivo experiments showed that MSC-RUNX1 treatment could promote tendon-bone healing and inhibit inflammatory response in rats. MSC-RUNX1 treatment also promoted angiogenesis at the tendon-bone healing site, while inhibiting osteoclast formation and promoting osteogenic differentiation. CONCLUSION: hUC-MSCs overexpressing RUNX1 can inhibit the formation of osteoclasts and differentiation of osteoblasts, promote angiogenesis and inhibit inflammation, thereby promoting tendon-bone healing after RCI.

Bibliometric and visualized analysis of arthroscopic treatment of acromioclavicular joint injury.

BACKGROUND: Since arthroscopy was discovered to treat acromioclavicular joint injury, people have had great interest and attention to this beautiful and minimally invasive operation, and related research has been increasing worldwide. At present, there is no bibliometric and visualized analysis in this field. The purpose of this study is to explore the research hotspots and trends of arthroscopic treatment of acromioclavicular joint injury through bibliometric and visualized analysis and look forward to the future development direction of clinical practice. METHODS: The publications on arthroscopic treatment of acromioclavicular joint injury diseases from its establishment to April 2023 were obtained from the Web of Science (WOS) Core Collection database. CiteSpace, VOSviewer, Scimago graphica and Origin were used for bibliometric and visualized analysis. RESULTS: This study included a total of 330 publications. The number of publications tends to increase every year. The USA has the most significant number of publications and citations. Imhoff AB is the most relevant scholar with the largest number of publications in this field, and the scholar with the highest citation and average citations is Mazzocca AD. Tech Univ Munich, Rush University and Charite are the three institutions with the greatest contribution. Tech Univ Munich, Rush University and Charite are the three institutions with the greatest contribution. In addition, "Arthroscopy-the Journal of Arthroscopic and Related Surgery" and "American Journal of Sports Medicine" are the institutions with the most significant number of publications and average citations, respectively. The most common keywords are "acromioclavicular joint dislocation," "arthroscopic resection," "arthroscopic reconstruction" and "coracoclavicular ligament." CONCLUSION: The number of publications shows a steady upward trend as a whole. However, there is still a lack of cooperation among countries, institutions and scholars around the world, so various countries, institutions and scholars need to strengthen academic exchanges and expand the field of cooperation, so as to promote further research and development in related fields. However, minimally invasive methods such as arthroscopy are still the hotspots and frontiers in the treatment of acromioclavicular joint injury in the future.

Analysis of risk factors for procedure-related hemorrhage in rotator cuff repair surgery under shoulder arthroscopy.

The present study aims to validate the methods of quantifying blood loss in arthroscopic rotator cuff repair and to investigate the correlation between blood loss and joint pain and joint function recovery. A total of 38 patients with unilateral rotator cuff injuries who underwent shoulder arthroscopy were analyzed in this study. Related information, including age, gender, blood pressure, body mass index (BMI), disease entity, comorbidity, joint release, and operating time, were collected into a spreadsheet. Serum hemoglobin and hematocrit (HCT) levels were obtained before the surgery and on the first and third days after the operation. The visual analog scale (VAS) score and the constant-Murley score of the shoulder joint were evaluated 1 year after the operation. Preoperative blood volume (PBV), red blood cell (RBC), hemoglobin (Hb), and HCT levels were significantly higher than those on postoperative day 1 and day 3. The average surgery-related blood loss was calculated to be 435.2 ±â€…53.6 mL during the surgery and the first postoperative day and 542.5 ±â€…63.0 mL during the surgery and the first 3 days after the surgery. The VAS score was significantly reduced 1 year after surgery. The multivariate linear regression analysis showed that joint release was a potential risk factor for predicting blood loss 1 or 3 days postoperatively. The actual blood loss from shoulder arthroscopy may be underestimated. The joint release was regarded as the leading risk factor for blood loss.

Robotic-assisted systems for the safe and reliable treatment of femoral neck fractures: retrospective cohort study.

BACKGROUND: Robots are being used in a wide range of surgical procedures. However, in clinical practice, the efficacy of orthopedic robotic-assisted treatment of femoral neck fractures is still poorly reported, particularly in terms of screw placement accuracy, femoral neck fracture healing rates and postoperative functional recovery. Moreover, there is a lack of comparative analysis between robot-assisted surgery and traditional surgical approaches. PURPOSE: The purpose of this study was to compare the clinical outcomes of patients with femoral neck fractures treated with TiRobot-assisted hollow screw fixation with those of patients with femoral neck fractures treated with traditional surgical approaches. METHODS: This study included 112 patients with femoral neck fracture who were treated from March 2017 to October 2021 with percutaneous hollow screw internal fixation. These included 56 cases in the TiRobot-assisted surgery group and 56 cases in the standard surgery group. After at least 1 year of follow-up, the treatment outcomes of the two groups were compared, including the amount of intraoperative bleeding, the duration of intraoperative fluoroscopy, the number of guide pin positioning adjustments, the length of hospital stay, the accuracy rate of screw placement, the final Harris Hip Score, the fracture healing rate, and the rate of femoral head necrosis. Statistical analysis software was used to process and analyze the result. RESULTS: The TiRobot-assisted group had a statistically significant improvement over the control group in terms of intraoperative bleeding, the duration of intraoperative fluoroscopy, the number of guide pin positioning adjustments, length of hospital stay, accuracy of screw placement and incidence of femoral head necrosis (P < 0.05). There was no statistically significant difference in time to surgery, final Harris hip score and fracture healing rate (P > 0.05). CONCLUSION: This study shows that TiRobot-assisted surgery has the advantages of short hospital stay, high safety, minimally invasive, high success rate of nail placement, and can reduce the amount of intraoperative radiation and the incidence of femoral head necrosis, thus achieving satisfactory clinical outcomes, and is worthy of clinical promotion.

The latest edition of WHO and ELN guidance and a new risk model for Chinese acute myeloid leukemia patients.

Objective: Diagnosis classification and risk stratification are crucial in the prognosis prediction and treatment selection of acute myeloid leukemia (AML). Here, we used a database of 536 AML patients to compare the 4th and 5th WHO classifications and the 2017 and 2022 versions of ELN guidance. Methods: AML patients were classified according to the 4th and 5th WHO classifications, as well as the 2017 and 2022 versions of the European LeukemiaNet (ELN) guidance. Kaplan-Meier curves with log-rank tests were used for survival analysis. Results: The biggest change was that 25 (5.2%), 8 (1.6%), and 1 (0.2%) patients in the AML, not otherwise specified (NOS) group according to the 4th WHO classification, were re-classified into the AML-MR (myelodysplasia-related), KMT2A rearrangement, and NUP98 rearrangement subgroups based on the 5th WHO classification. Referring to the ELN guidance, 16 patients in the favorable group, six patients in the adverse group, and 13 patients in the intermediate group based on the 2017 ELN guidance were re-classified to the intermediate and adverse groups based on the 2022 ELN guidance. Regrettably, the Kaplan-Meier curves showed that the survival of intermediate and adverse groups could not be distinguished well according to either the 2017 or 2022 ELN guidance. To this end, we constructed a risk model for Chinese AML patients, in which the clinical information (age and gender), gene mutations (NPM1, RUNX1, SH2B3, and TP53), and fusions (CBFB::MYH11 and RUNX1::RUNX1T1) were included, and our model could help divide the patients into favorable, intermediate, and adverse groups. Conclusion: These results affirmed the clinical value of both WHO and ELN, but a more suitable prognosis model should be established in Chinese cohorts, such as the models we proposed.

IFN-α-2b Reduces Postoperative Arthrofibrosis in Rats by Inhibiting Fibroblast Proliferation and Migration through STAT1/p21 Signaling Pathway.

Objective: To investigate the effect of IFN-α-2b in preventing postoperative arthrofibrosis in rats, its antiproliferation effect on fibroblasts in vitro, and its molecular mechanism. Methods: The rat model of arthrofibrosis was established and treated with different concentrations of drugs. Knee specimens were collected for histological and immunohistochemical staining to observe the effect of IFN-α-2b on arthrofibrosis in rats. The biological information was further mined according to the database data, and the possible regulatory mechanism of IFN-α-2b on fibroblasts was analyzed. The inhibitory effect of IFN-α-2b on fibroblast proliferation and migration in vitro was detected by cell counting kit-8 (CCK-8), immunofluorescence analysis, cell cycle test, EdU assay, wound healing test, and Transwell method, and the analysis results were verified by Western blotting method. Results: The test results of rat knee joint specimens showed that IFN-α-2b significantly inhibited the degree of fibrosis after knee joint surgery, the number of fibroblasts in the operation area was less than that of the control group, and the expression of collagen and proliferation-related proteins decreased. In vitro experimental results show that IFN-α-2b can inhibit the proliferation and migration of fibroblasts. According to the results of database analysis, it is suggested that the STAT1/P21 pathway may be involved, and it has been verified and confirmed by Western blotting and other related methods. Conclusion: IFN-α-2b can reduce surgery-induced arthrofibrosis by inhibiting fibroblast proliferation and migration, which may be related to the regulation of STAT1/p21 signaling pathway.

Lung specific homing of diphenyleneiodonium chloride improves pulmonary fibrosis by inhibiting macrophage M2 metabolic program.

INTRODUCTION: Pulmonary fibrosis (PF) is a fatal disease with a variable and unpredictable course. Effective clinical treatment for PF remains a challenge due to low drug accumulation in lungs and imbalanced polarization of pro/anti-fibrotic macrophages. OBJECTIVES: To identify the alteration of immunometabolism in the pulmonary macrophages and investigate the feasibility of specific inhibition of M2 activation of macrophages as an effective anti-PF strategy in vivo. METHODS: The high-content screening system was used to select lung-specific homing compounds that can modulate macrophage polarization. Imaging mass spectrometry (IMS) conjugated with chemical proteomics approach was conducted to explore the cells and proteins targeted by diphenyleneiodonium chloride (DPI). A bleomycin-induced fibrotic mouse model was established to examine the in vivo effect of DPI. RESULTS: Pulmonary macrophages of PF at late stage exhibited predominantly the M2 phenotype with decreased glycolysis metabolism. DPI was demonstrated to inhibit profibrotic activation of macrophages in the preliminary screening. Notably, IMS conjugated with chemical proteomics approach revealed DPI specifically targeted pulmonary macrophages, leading to the efficient protection from bleomycin-induced pulmonary fibrosis in mice. Mechanistically, DPI upregulated glycolysis and suppressed M2 programming in fibrosis mice, thus resulting in pro-fibrotic cytokine inhibition, hydroxyproline biosynthesis, and collagen deposition, with a concomitant increase in alveolar airspaces. CONCLUSIONS: DPI mediated glycolysis in lung and accordingly suppressed M2 programming, resulting in improved lung fibrosis.

Oxidative Stress Amplifiers as Immunogenic Cell Death Nanoinducers Disrupting Mitochondrial Redox Homeostasis for Cancer Immunotherapy.

Reactive oxygen species (ROS)-induced oxidative stress in the endoplasmic reticulum (ER) is generally believed to be an important prerequisite for immunogenic cell death (ICD) which can trigger antitumor immune responses for cancer immunotherapy. However, thus far, little is known between the oxidative stress in a certain organelle other than ER and ICD. Herein, polymers for preparing ROS-responsive nanoparticles (NP-I-CA-TPP) with mitochondrial targeting performance as ICD nanoinducers are designed. It is believed that NP-I-CA-TPP can target mitochondria which are extremely important organelles intimately involved in cellular stress signaling to play an important role in the induction of ICD. NP-I-CA-TPP can amplify cinnamaldehyde (CA)-induced ROS damage by iodo-thiol click chemistry-mediated glutathione depletion in cancer cells. Finally, NP-I-CA-TPP is shown to disrupt mitochondrial redox homeostasis, amplify mitochondrial oxidative stress, promote cancer cell apoptosis via inducing ICD, and triggering the body's antitumor immune response for cancer immunotherapy.

Accuracy and feasibility with AI-assisted OCT in retinal disorder community screening.

Objective: To evaluate the accuracy and feasibility of the auto-detection of 15 retinal disorders with artificial intelligence (AI)-assisted optical coherence tomography (OCT) in community screening. Methods: A total of 954 eyes of 477 subjects from four local communities were enrolled in this study from September to December 2021. They received OCT scans covering an area of 12 mm × 9 mm at the posterior pole retina involving the macular and optic disc, as well as other ophthalmic examinations performed using their demographic information recorded. The OCT images were analyzed using integrated software with the previously established algorithm based on the deep-learning method and trained to detect 15 kinds of retinal disorders, namely, pigment epithelial detachment (PED), posterior vitreous detachment (PVD), epiretinal membranes (ERMs), sub-retinal fluid (SRF), choroidal neovascularization (CNV), drusen, retinoschisis, cystoid macular edema (CME), exudation, macular hole (MH), retinal detachment (RD), ellipsoid zone disruption, focal choroidal excavation (FCE), choroid atrophy, and retinal hemorrhage. Meanwhile, the diagnosis was also generated from three groups of individual ophthalmologists (group of retina specialists, senior ophthalmologists, and junior ophthalmologists) and compared with those by the AI. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated, and kappa statistics were performed. Results: A total of 878 eyes were finally enrolled, with 76 excluded due to poor image quality. In the detection of 15 retinal disorders, the ROC curve comparison between AI and professors' presented relatively large AUC (0.891-0.997), high sensitivity (87.65-100%), and high specificity (80.12-99.41%). Among the ROC curve comparisons with those by the retina specialists, AI was the closest one to the professors' compared to senior and junior ophthalmologists (p < 0.05). Conclusion: AI-assisted OCT is highly accurate, sensitive, and specific in auto-detection of 15 kinds of retinal disorders, certifying its feasibility and effectiveness in community ophthalmic screening.

Sinensetin attenuates IL-1ß-induced cartilage damage and ameliorates osteoarthritis by regulating SERPINA3.

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, synovial hyperplasia and osteophyte formation as the main pathological manifestations. Age, mechanical stress and inflammation are the main factors that induce joint degeneration in the pathogenesis of OA. Sinensetin (SIN) is a natural flavonoid with anti-inflammatory and antioxidant properties. This study aims to investigate the effect of SIN on OA. We have investigated the anti-inflammatory and chondroprotective effects of SIN on IL-1ß-induced human OA chondrocytes and a rat OA model. In vitro, human chondrocytes were induced by 5 ng mL-1 IL-1ß and treated with different concentrations of SIN. The results suggest that SIN can inhibit IL-1ß-induced overproduction of pro-inflammatory mediators in human OA chondrocytes, including COX2, iNOS, TNF-α and IL-6, and also reduce the production of MMP13 and MMP9, thus protecting the degradation of the extracellular matrix. In addition, SIN can inhibit the activation of NF-κB by regulating the expression of SERPINA3. In an in vivo experiment, rats were randomly divided into 3 groups, namely the sham operation group, OA model group and SIN group, and were given normal saline or 20 mg kg-1 SIN, respectively. The knee cartilage tissue was removed 6 weeks after surgery for analysis and detection, and our studies have shown that SIN can effectively delay the progression of OA in rats and protect cartilage. In conclusion, our study shows that SIN has good application potential in the treatment of OA.

DL-3-N-Butylphthalide Promotes Cartilage Extracellular Matrix Synthesis and Inhibits Osteoarthritis Development by Regulating FoxO3a.

Osteoarthritis (OA) has been reported as a progressive disease in the elderly, primarily characterized by degenerated articular cartilage. There has been no satisfactory drug for the treatment of OA. DL-3-n-butylphthalide (NBP), a small molecule compound extracted from celery seeds, may have antiapoptotic, antioxidant, and anti-inflammatory activities in numerous studies. However, the effects of NBP on OA and its mechanisms have been rarely reported. In this study, the effect of NBP on OA in vitro and in vivo and its possible mechanism were investigated. The results showed that NBP injection into the knee joint inhibited osteoarthritis development in a rat model of osteoarthritis induced by DMM+ACLT. NBP could increase the expressions of extracellular matrix-related components (such as type II collagen, aggrecan, proteoglycan 4, and SRY-box 9) in human osteoarthritic chondrocytes and cartilage explants. Moreover, NBP promoted the expressions of SOD and CAT. NBP upregulated the expression of FoxO3a by inhibiting the PI3K/AKT pathway, which subsequently inhibited the apoptosis of human OA chondrocytes. In conclusion, NBP promotes cartilage extracellular matrix synthesis and inhibits osteoarthritis development and the underlying mechanism related to the activation of FoxO3a.

Estrogen alleviates post-traumatic osteoarthritis progression and decreases p-EGFR levels in female mouse cartilage.

OBJECTIVE: To investigate the effect of estrogen on the progression of post-traumatic osteoarthritis (PTOA) in mice and its possible mechanism. METHODS: Twelve-week-old ICR mice were divided into Group A (female control group), group B (ovariectomized(OVX) group), group C (OVX group supplemented with estrogen), and group D (male group) by destabilization of the medial meniscus (DMM)or sham operation. Safranin O staining was performed at 8 weeks and 12 weeks after operation, and the degree of articular cartilage lesion was evaluated using Mankin score. Twelve weeks after the operation, tissue sections were stained to analyze the matrix metalloproteinase 13(MMP13), phosphorylated epidermal growth factor receptor (p-EGFR) expression and apoptosis of chondrocytes. RESULTS: Decreased estrogen can significantly increase the weight of mice in female mice. The degree of cartilage damage in the knee joint on the DMM side of female mice was significantly severer than that on the Sham side. The DMM side also showed higher MMP13 expression and increased apoptotic chondrocytes. The degree of cartilage damage in the knee joint on the DMM side of female mice was significantly reduced after estrogen supplementation, and cartilage damage in the knee joint on the DMM side of female mice was less serious than that of male mice. As estrogen levels decreased, the severity of cartilage erosion in the knee joint on the DMM side was aggravated, and p-EGFR expression in the cartilage surface was also higher in female mice contrast to that in male mice. However, minimal changes in p-EGFR expression in the cartilage surface of bilateral knee joints of male mice were observe. CONCLUSION: Estrogen has a regulatory effect on PTOA and its inhibits the expression of p-EGFR in cartilage on the knee joint surface and has a protective effect on articular cartilage in female mice.

Mitochondrial metabolism mediated macrophage polarization in chronic lung diseases.

As the first line of defence in the lung, alveolar macrophage contributes to maintaining lung immune homoeostasis. Characterized by the heterogeneity and plasticity, macrophages polarize into two pro-inflammatory and anti-inflammatory phenotypes regarding the biological and pathological environment. In the past decade, numerous studies have revolutionized the relationship between cellular metabolism and macrophage functions. Mitochondria dysfunctions, which results in altered cellular metabolic profile, were observed in the alveolar macrophages during chronic lung diseases. In addition, alveolar macrophages adapt metabolic reprogramming to produce an immune response against the pathogens. Here, we outline the role of mitochondria in the development of macrophage phenotypes and functions and highlight the mitochondrial dysfunction in the setting of chronic lung diseases. Lastly, we emphasize the therapeutic relevance of targeting metabolic pathways in alveolar macrophages, which may shed light on developing novel strategies against chronic lung diseases.

MicroRNA-143 expression inhibits the growth and the invasion of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common malignant tumor, which occurs in the metaphysis of the long diaphysis from mesenchymal tissue. Previous studies have indicated that expression of microRNA-143 (miR-143) could affect cancer cell proliferation, migration and invasion. The present research was performed to figure out whethermiR-143 expression inhibits the growth and the invasion of OS. METHODS: We conducted a literature search in the electronic databases of Medline, Embase, Web of Science, and the Cochrane Library, SinoMed, WanFang, China national knowledge infrastructure (CNKI) until January 2022. We used Review Manager 5.3 software to conduct our research. RESULTS: Twelve eligible articles were included, 5 articles were reported outcomes about mice, 11 articles were reported outcomes about human. The results of mice demonstrated that the miR-143 group had significantly better results in tumor volume, tumor weight and survival rate. The results of human demonstrated that the high level of miR-143 group had significantly better results in the 3-year, 4-year, and 5-year survival rate, lung metastasis and tumor grade. CONCLUSIONS: MiR-143 has potentially important value in the treatment and prognosis of OS. However, more reliable animal and clinical trials are needed before miR-143 based therapies can be transferred from animal studies to human applications.