Association between dietary folate intake and the risk of osteoporosis in adults: a cross-sectional study.

BACKGROUND: Increased intake of specific vitamins has been linked to a decreased prevalence of osteoporosis. However, the association between dietary folate intake and the risk of osteoporosis in the general population remains incompletely understood. Therefore, we aimed to determine the association between dietary folate intake and the risk of osteoporosis in the general population of the USA. METHODS: In this cross-sectional study, data from the National Health and Nutrition Examination Survey (2017-2020) were collected. Osteoporosis was considered to be indicated by a bone mineral density greater than 2.5 standard deviations below the mean of the young adult reference group. Dietary folate intake was measured by a 24-hour dietary recall. Multivariate logistic regression models and restricted cubic spline models were used. RESULTS: The study included 2297 participants (mean age: 63.69 ± 0.35 years), 49.92% of whom were female. In the general population, increased dietary folate intake was directly associated with a decreased risk of osteoporosis (P for trend = 0.005). In the age > 60 years and female subgroups, folate intake was inversely associated with the risk of osteoporosis (P for trend < 0.001). The dose‒response curve suggested that this association was nonlinear (P for nonlinearity = 0.015). CONCLUSIONS: Our cross-sectional study provides initial insights into the inverse association between dietary folate intake and the risk of osteoporosis in the general U.S. POPULATION: Further research is needed to confirm these associations.

Safety and feasibility of single-port nephroscopy combined with a needle electrode technique to treat dorsal SRCs.

Objective The aim of this study was to explore the safety and feasibility of single-port nephroscopy combined with a needle electrode technique to unroof single dorsal simple renal cysts (SRCs). Methods This was a retrospective analysis of the clinical data for 18 patients with single dorsal SRCs treated with single-port nephroscopy and a needle electrode technique at Zhongshan City People's Hospital from August 2021 to August 2022. The basic information included the cyst condition, surgical methods and recurrence rate, and follow-up was conducted with CT imaging. Results The surgery was successful in all 18 patients. The duration of surgery ranged from 24-46 minutes, with an average of 35.83±1.62 minutes; the intraoperative bleeding volume ranged from 2-20 ml, with an average of 9.0±1.3 ml; and the visual analog scale (VAS) score within 24 hours after surgery ranged from 1-6 points, with an average of 2.72±0.36 points. There were no significant postoperative complications, such as bleeding, urinary fistula, or infection. All drainage tubes were removed on the first day after surgery. After 1 year of postoperative follow-up, one patient experienced recurrence, for a recurrence rate of 5.6%. Conclusion Single-port nephroscopy combined with a needle electrode technique is a safe, feasible, and effective minimally invasive surgical approach for treating single dorsal SRCs.

Hedgehog signaling promotes multidrug resistance by regulation of ABC transporters in oral squamous cell carcinoma.

BACKGROUND: Multidrug resistance (MDR) is one of the reasons for treatment failure in oral squamous cancer patients; however, the MDR mechanisms remain elusive. METHODS: Two human oral squamous cell carcinoma (OSCC) cell lines, CAL27 and SCC9, were analyzed by stepwise selection upon exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) for MDR cell line establishment, and cell viability was analyzed by CCK8 assays. Transcriptomes of the CAL27 and CAL27-MDR cells were analyzed by RNA-seq assay. The molecules in Sonic hedgehog (Shh) signal pathway and MDR related pathway were selected for validation by qRT-PCR and Western blot. Human OSCC tissues were applied for immunohistochemical and clinicopathological analysis. RESULTS: The OSCC-MDR cell lines with resistance to 5-FU and CDDP were successfully established. Protein expression levels of ATP-binding cassette (ABC) transporter ABCC1 and ABCG2 were increased 1.6-fold and 2.1-flod, respectively, in OSCC specimen from the patients with chemotherapy. The RNA-seq assay speculated the activation of Hedgehog (Hh) signaling with the upregulation of SHH, PTCH1, and SMO in OSCC-MDR cells as compared with OSCC cells. Furthermore, immunohistochemical studies confirmed that the high expression of SHH, PTCH1, and SMO in OSCC patients was significantly associated with chemotherapy. Overexpression of SHH increased the chemoresistance in OSCC cells, while the mRNA expression levels of PTCH1 and ABCG2 were increased in OSCC cells upon stimulation with recombinant SHH protein. CONCLUSIONS: These results revealed that the activation of Hh signaling pathway regulating ABC transporters is associated MDR in OSCC.

Constipation and risk of urinary incontinence in women: a meta-analysis.

INTRODUCTION AND HYPOTHESIS: Constipation is reported to be associated with urinary incontinence. However, the reported results have been inconsistent and contradictory. To evaluate the association between constipation and urinary incontinence in women, we performed a meta-analysis. METHODS: A comprehensive search based on PubMed, EMBASE, and the Cochrane Library was performed up to July 2018 for eligible studies in relation to the influence of constipation on urinary incontinence in women. A random-effect model was used to calculate the pooled odds risk (OR) and corresponding 95% confidence interval (CI). RESULTS: A total of 16 observational studies with 35,629 participants and 6054 urinary incontinence patients were identified in the meta-analysis. Constipation was significantly associated with the risk of urinary incontinence in women (OR 2.46, 95% CI 1.79-3.38). CONCLUSIONS: This meta-analysis suggests that constipation is significantly associated with urinary incontinence risk in women. However, further well-designed, large-scale prospective studies are needed to clarify the causality.

Systematic analysis of long non-coding RNA and mRNA profiling using RNA sequencing in the femur and muscle of ovariectomized rats.

OBJECTIVE: To investigate the expression profile of lncRNAs in bone and skeletal muscle of ovariectomized (OVX) rats. METHODS: Six-month-old female Sprague-Dawley (SD) rats were divided into OVX group (ovariectomized, n=12) and sham group (sham-operated, n=12). After 12 weeks, RNA-seq was used to analyze the differential expression of lncRNAs and mRNAs in femur and quadriceps between two groups. Dys-regulated expression of lncRNAs was confirmed by qRT-PCR. The cis and trans-regulatory functions were analyzed to determine their function and biological processes. Lastly, GO and KEGG analyses were performed to assess the biological relevance of genes in each profile. RESULTS: A total of 17 lncRNAs and 440 mRNAs were differentially expressed in the femur. Thirteen lncRNAs and 292 mRNAs were differentially expressed in the quadriceps. qRT-PCR results were in consistent with the RNA-seq data. Among them, ENSRNOT00000090777 was found in both femur and quadriceps samples. Bioinformatics analysis found that LNC_004549 participated in the differentiation of skeletal and skeletal muscle. CONCLUSIONS: The expression profile of lncRNAs was significantly altered in femur and quadriceps of OVX rat models, which may offer new insights into pathogenesis of osteoporosis and sarcopenia and potentially provide novel therapeutic targets.

Ginsenoside Rh2 Inhibits Angiogenesis in Prostate Cancer by Targeting CNNM1.

To explore the molecular mechanism by which ginsenoside Rh2 (G-Rh2) inhibits prostate cancer by regulating vascular growth. Different concentrations of G-Rh2 with three prostate cancer cell lines (LNCaP, PC3 and DU145) were transplanted in nude mice, and tumor mass volume was measured over time. LNCaP, PC3 and DU145 were co-cultured with vascular endothelial cells to determine the optimal concentration of G-Rh2 by MTT assay. LNCaP, PC3 and DU145 were cultured under the selected concentration (0, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL) of G-Rh2, and the expression levels of CD31, VEGF, PDGF and CNNM1 detected by qRT-PCR and western blot. The expression pattern of CD31 was detected in CNNM1 overexpressed and knockout LNCaP, PC3 and DU145 cells under G-Rh2. G-Rh2 significantly inhibited the growth of all three prostate cancer cell lines in the dorsum of nude mice (P <0.05), and the increment rate of vascular endothelial cells co-cultured with LNCaP, PC3 and DU145 (P <0.05). The expression of CD31, VEGF, PDGF and CNNM1 genes in LNCaP, PC3 and DU145 cells was inhibited by G-Rh2. Overexpression of CNNM1 reversed the inhibitory effect of G-Rh2 on the expression of CD31 in these cells (P <0.05), while the function of knockout of CNNM1 and the inhibitory effect of G-Rh2 appeared to be similar (P <0.05). In conclusion, G-Rh2 inhibited prostate cancer growth by inhibiting its angiogenesis through decreasing the expression of CNNM1 in the cancer cells.

Hippocampal neuron loss and astrogliosis in medial temporal lobe epileptic patients with mental disorders.

Hippocampal neuron loss and reactive astrogliosis are pathological features of medial temporal lobe epilepsy. Here, the expression of hippocampal astrogliosis-associated genes are studied in subjects with medial temporal lobe epilepsy and mental disorders (such as depression, anxiety and psychiatric comorbidities). The relationship between functional changes in hippocampus astrocytes and concurrent mental disorders are discussed. Nissl staining identified medial temporal lobe epilepsy-induced neuronal loss in the CA1 region of hippocampus. Quantitative real-time polymerase chain reaction and immunofluorescence technology were used to detect hippocampus glial fibrillary acidic protein, metallothionein, and aquaporin-4. The hippocampus area of subjects with medial temporal lobe epilepsy (with or without mental disorders) were smaller than the control group. Hippocampal neuronal loss and astrogliosis were more obvious in groups of medial temporal lobe epileptic patients with mental disorders. Relative protein levels of glial fibrillary acidic protein, metallothionein-I/II, and aquaporin-4 were significantly higher in subjects with medial temporal lobe epilepsy than seen in controls. Medial temporal lobe epileptic patients with mental disorder or depression had elevated metallothionein-I/II protein level when compared to controls and medial temporal lobe epileptic patients without mental disorder. Protein levels of glial fibrillary acidic protein and aquaporin-4 in medial temporal lobe epileptic patients with mental disorders were significantly lower than that in medial temporal lobe epileptic patients with no mental disorder. It is concluded that functional changes in hippocampus astrocytes are associated with mental disorders in medial temporal lobe epileptic patients and the astrogliosis-related genes of glial fibrillary acidic protein, metallothionein-I/II and aquaporin-4, are involved in this process.

Effects of bariatric surgery on pelvic floor disorders in obese women: a meta-analysis.

PURPOSE: Obesity is an established risk factor for pelvic floor disorders (PFD) but the effects of bariatric surgery on PFD are uncertain. This meta-analysis was conducted to evaluate the effects of bariatric surgery on PFD in obese women. METHODS: A systematic search of PubMed, Cochrane Library, CNKI and CBM databases up to October 2016 was performed, and studies reporting pre-operative and post-operative outcomes in obese women undergoing bariatric surgery were included. The Pelvic Floor Distress Inventory (PFDI-20), the Pelvic Floor Incontinence Questionnaire (PFIQ-7), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, Female Sexual Function Index and the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form score were used for evaluating pelvic floor dysfunction after bariatric surgery. RESULTS: Eleven cohort studies were finally included. Pooled results revealed that bariatric surgery was associated with a significant improvement in PFD for obese women on the whole [PFDI-20: SMD = 0.89, 95% CI (0.44, 1.34), P < 0.001; PFIQ-7: SMD = 1.23, 95% CI (0.17, 2.29), P = 0.023]. In the subscale analysis, there was significant improvement in urinary incontinence and pelvic organ prolapse. However, no significant improvement was found in fecal incontinence and sexual function. CONCLUSIONS: Bariatric surgery is associated with significant improvement in urinary incontinence, and has a benefit on pelvic organ prolapse for obese women. However, there is no significant improvement in fecal incontinence and sexual function. Further multi-center, large-scale and longer-term randomized controlled trials are needed to confirm these results.

Elevated CCL2/MCP-1 Levels are Related to Disease Severity in Postmenopausal Osteoporotic Patients.

BACKGROUND: Chemokine (C-C) ligand-2 (CCL2), also named monocyte chemoattractant protein 1 (MCP-1), is an important chemotactic factor involved in a wide range of diseases. Recent studies have shown that CCL2/MCP-1 plays crucial roles in the osteoclastogenic process. The current study was performed to measure serum CCL2 levels in postmenopausal osteoporotic patients and investigate the relationship between CCL2 concentrations in serum and disease severity in postmenopausal osteoporotic patients. METHODS: A total of 62 postmenopausal osteoporotic female patients (PMOP group), 68 postmenopausal non-osteoporotic female patients (PMNOP group), and 65 healthy women of childbearing age (Control group) were enrolled in the study. The calcaneal quantitative ultrasound was utilized to conduct bone mineral density (BMD) measurements, confirmed at the left femoral neck, greater trochanter, total hip, and L1 - L4 lumbar spine by dual energy X-ray absorptiometry (DXA). Serum CCL2, TNF-α as well as IL-6 levels were measured with enzyme-linked immunosorbent assay. Estrogen-2 (E2) was measured with radioimmunoassay. The Visual Analogue Scores (VAS) was utilized to assess the extent of pain in PMOP. RESULTS: We demonstrated for the first time that CCL2 levels were increased in postmenopausal women compared with controls. We also found that elevated CCL2 levels were linked with decreased BMD and attenuated E2 concentrations. In addition, CCL2 levels were positively correlated with inflammation markers TNF-α, IL-6, and VAS scores. CONCLUSIONS: CCL2 in serum serves as a potential biomarker for reflecting disease severity in postmenopausal osteoporotic patients. Therapeutic interventions that target CCL2 and its related signaling pathways in order to delay osteoporosis development deserve further study.

Research on Medical Image Segmentation Method Based on Improved U-Net3.

Computer assisted diagnostic technology has been widely used in clinical practice, specifically focusing on medical image segmentation. Its purpose is to segment targets with certain special meanings in medical images and extract relevant features, providing reliable basis for subsequent clinical diagnosis and research. However, because of different shapes and complex structures of segmentation targets in different medical images, some imaging techniques have similar characteristics, such as intensity, color, or texture, for imaging different organs and tissues. The localization and segmentation of targets in medical images remains an urgent technical challenge to be solved. As such, an improved full scale skip connection network structure for the CT liver image segmentation task is proposed. This structure includes a biomimetic attention module between the shallow encoder and the deep decoder, and the feature fusion proportion coefficient between the two is learned to enhance the attention of the overall network to the segmented target area. In addition, based on the traditional point sampling mechanism, an improved point sampling strategy is proposed for characterizing medical images to further enhance the edge segmentation effect of CT liver targets. The experimental results on the commonly used combined (CT-MR) health absolute organ segmentation (CHAOS) dataset show that the average dice similarity coefficient (DSC) can reach 0.9467, the average intersection over union (IOU) can reach 0.9623, and the average F1 score can reach 0.9351. This indicates that the model can effectively learn image detail features and global structural features, leading to improved segmentation of liver images.

Tracking Chinese Online Activity and Interest in Osteoporosis Using the Baidu Index.

Introduction China's most widely used online search engine, Baidu (Baidu, Inc., Beijing, China), has developed a data collection and analysis tool called the Baidu Index for tracking Internet search trends. The purpose of this study was to examine the utility of the Baidu Index in tracking online osteoporosis information-seeking behavior and comprehending the traits and concerns of the Chinese population. Methods We used the search term "osteoporosis" for the Baidu Index for the years 2018-2022. The geographic and demographic distributions, search volumes, and demand maps were recorded. Results The popularity of the search term "osteoporosis" has increased over time. The search was mostly conducted among women aged 20-39 in northern China. The demand map revealed that the most significant concerns are related to the diagnosis, treatment, and etiology of osteoporosis. Conclusion The Baidu Index is a valuable tool for tracking online health information-seeking behavior among Chinese netizens. Online search trend data appears to reflect the geographic and demographic aspects of osteoporosis to a certain extent.

Identification and immunological role of cuproptosis in osteoporosis.

Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we intended to investigate the molecular clusters related to the cuproptosis in osteoporosis and to construct a predictive model. Methods: we investigated the expression patterns of cuproptosis regulators and immune signatures in osteoporosis based on the GSE56815 dataset. Through analysis of 40 osteoporosis samples, we investigated molecular clustering on the basis of cuproptosis--related genes, together with the associated immune cell infiltration. The WGCNA algorithm was applied to detect cluster-specific differentially expressed genes. Afterwards, the optimum machine model was selected by calculating the performance of the support vector machine model, random forest model, eXtreme Gradient Boosting and generalized linear model. Nomogram, decision curve analysis, calibration curves, and the GSE7158 dataset was utilizing to confirm the prediction efficiency. Results: Differences between osteoporotic and non-osteoporotic controls confirm poorly adjusted copper death-related genes and triggered immune responses. In osteoporosis, two clusters of molecules in connection with copper death proliferation were outlined. The assessed levels of immune infiltration showed prominent heterogeneity between the different clusters. Cluster 2 was characterized by a raised immune score accompanied with relatively high levels of immune infiltration. The functional analysis we performed showed a close relationship between the different immune responses and specific differentially expressed genes in cluster 2. The random forest machine model showed the optimum discriminatory performance due to relatively low residuals and root mean square errors. Finally, a random forest model based on 5 genes was built, showing acceptable performance in an external validation dataset (AUC = 0.750). Calibration curve, Nomogram, and decision curve analyses also evinced fidelity in predicting subtypes of osteoporosis. Conclusion: Our study identifies the role of cuproptosis in OP and essentially illustrates the underlying molecular mechanisms that lead to OP heterogeneity.

Analysis of the origin and invasion of prostate cancer from autopsy and radical prostatectomy specimens.

Background: Without a pseudocapsule, prostate cancer is invasive in volume growth and has some regularity in spatial distribution. Our study aims to explore the specific origin location, invasive characteristics, and morphology of prostate cancer. Methods: Ninety-eight clinical specimens with tumor volume equal to or less than one-third of the organ volume and 111 autopsy specimens were retrospectively analyzed. The origin location and invasion of prostate cancer in four horizontal quadrants and 11 vertical slides were demonstrated. In addition, the median maximum anteroposterior, left-right, horizontal, and vertical diameters of lesions were compared, and the spatial morphology of lesions was described. Results: There were 335 lesions in the autopsy and clinical specimens. There was no significant difference in the distribution of lesions confined to the horizontal quarter quadrant (P=0.064). The number of lesions with a single positive slide above the apex 0.5-1.4 cm was 75 (49.7%). No significant difference was found when compared with the maximum vertical and horizontal diameters (P=0.421). However, the maximum left-right and horizontal diameters were longer than the maximum anteroposterior diameter (P=0.046 and P<0.001). The number of lesions with a tumor area that decreased from the center to both sides was 85 (46.2%) and decreased from the center to one side was 81 (44.0%). Conclusions: Approximately 50% of the lesions originated from the apex above 0.5-1.4 cm. The invasive tendency of prostate cancer was consistent in the horizontal and vertical dimensions but less so in the anteroposterior direction. About ninety percent of lesions with tumor area decreased from the center to both sides or one side.

The Application of Organoids in the Research of Skeletal Diseases: Current Status and Prospects.

Organoids, which are clumps of cells formed after in vitro 3D culture utilizing autologous tissue and stem cells, possess the 3D structure and corresponding functional and genetic features of the original tissue and organ. This model has immense potential in modeling the ontogeny of specific organismal organs, as well as in drug screening and studying molecular mechanisms. The newly developed concept of bone organoids, a special type of complex hard tissues that can be created in vitro using tissue engineering 3D culture technology, mimics the complex biological functions of bone tissue in vivo. These bone organoids are highly useful in elucidating the regulatory mechanisms of bone regeneration, screening tissue engineering materials, and promoting bone regeneration and repair. They offer promising applications in bone regeneration research.

Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia.

Blockade of the interaction of the immune checkpoint receptor programmed cell death protein (PD)-1 and its ligand PD-L1 has been found to be a promising cancer treatment. Our previous studies identified that nABPD1 competed with PD-L1 to bind PD-1. The aim of this study was to evaluate the efficacy and safety of anti-tumor immunotherapy of ICIK cells conjugated with peptides in vivo and in vitro. Here, we synthesized the nABPD1 derivatives SBP1 and SBP2 and showed that their binding efficiency to PD-1-positive improving cytokine-induced killer (ICIK) cells was 98 and 82%, respectively. The cytotoxicity of ICIK cells to T-cell acute lymphoblastic leukemia (T-ALL) cells was increased by conjugating with SBP1 or SBP2, which was 2 times higher than that of ICIK cells alone. Furthermore, mice experiments showed that the fluorescence intensity of leukemia cells in T-ALL xenograft models was reduced by more than 95%, indicating that the peptides enhanced the therapeutic effect in vivo, while morphological evaluations showed that the peptides had no toxicity to important organs. Therefore, peptide-cell conjugates (PCCs) may be a novel method to improve the efficacy of cancer immunotherapy by blocking PD-1 in T-ALL patients.

Identification of a Potential MiRNA-mRNA Regulatory Network for Osteoporosis by Using Bioinformatics Methods: A Retrospective Study Based on the Gene Expression Omnibus Database.

Introduction: As a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass, impairment of bone microstructure, and a high global morbidity rate. There is increasing evidence that microRNAs (miRNAs) are associated with the pathogenesis of OP. Weighted gene co-expression network analysis (WGCNA) is a systematic method for identifying clinically relevant genes involved in disease pathogenesis. However, the study of the miRNA-messenger RNA (mRNA) regulatory network in combination with WGCNA in OP is still lacking. Methods: The GSE93883 and GSE7158 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs) and differentially expressed genes (DEGs) were analyzed with the limma package. OP-related miRNAs from the most clinically relevant module were identified by the WGCNA method. The overlap of DE-miRNAs and OP-related miRNAs was identified as OP-related DE-miRNAs. Both upstream transcription factors and downstream targets of OP-related DE-miRNAs were predicted by FunRich. An intersection of predicted target genes and DEGs was confirmed as downstream target genes of OP-related DE-miRNAs. With the use of clusterProfiler in R, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed on target genes. Finally, both the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed and analyzed. Results: A total of 79 OP-related DE-miRNAs were obtained, most of which were predicted to be regulated by specificity protein 1 (SP1). Subsequently, 197 downstream target genes were screened out. The target genes were enriched in multiple pathways, including signaling pathways closely related to the onset of OP, such as Ras, PI3K-Akt, and ErbB signaling pathways. Through the construction of the OP-related miRNA-mRNA regulatory network, a hub network that may play a prominent role in the formation of OP was documented. Conclusion: By using WGCNA, we constructed a potential OP-related miRNA-mRNA regulatory network, offering a novel perspective on miRNA regulatory mechanisms in OP.

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy.

PURPOSE: The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells. MATERIALS AND METHODS: nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro. RESULTS: A high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 µM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells. CONCLUSION: nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

Exploring the effect of the "quaternary regulation" theory of "peripheral nerve-angiogenesis-osteoclast-osteogenesis" on osteoporosis based on neuropeptides.

Osteoporosis is a common bone metabolic disease among the middle-aged and elderly, with its high incidence rate and a major cause of disability and mortality. Early studies found that bone metabolic homeostasis is achieved through osteogenesis-osteoclast coupling. Although current anti-osteoporosis drugs can attenuate bone loss caused by aging, they present specific side effects. With the discovery of CD31hi Emcnhi blood vessels in 2014, the effect of H-type blood vessels on bone metabolism has been valued by researchers, and the ternary regulation theory of bone metabolism of "Angiogenesis-Osteoclast-Osteogenesis" has also been recognized. Nowadays, more studies have confirmed that peripheral nerves substantially impact bone metabolism. However, due to the complex function of peripheral nerves, the crosstalk mechanism of "Peripheral nerve-Angiogenesis-Osteoclast-Osteogenesis" has not yet been fully revealed. Neuropeptide serves as signaling molecules secreted by peripheral nerves that regulate blood vessels, osteoblasts, and osteoclasts' functions. It is likely to be the breakthrough point of the quaternary regulation theory of "Peripheral nerve-Angiogenesis-Osteoclast-Osteogenesis". Here, we discuss the effect of peripheral nerves on osteoporosis based on neuropeptides.

Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway.

Background: Postmenopausal osteoporosis (PMOP) is the most common primary osteoporosis, which is prone to fractures and affect the health and quality of life of the elderly and even shorten their lifetime. Traditional Chinese medicine can not only effectively improve osteoporosis and reduce fracture rate, but also have tonifying and analgesic effects. The purpose of this study was to investigate the effects of Zhuanggu Zhitong (ZGZT) Capsule on autophagy related genes and proteins in PMOP rats, so as to elucidate the molecular mechanism of tonifying deficiency and regulating stasis in the treatment of osteoporosis and analgesia. Methods: The PMOP rat model was established by bilateral oophorectomy, and then the rats were randomly divided into control group, PMOP group, PMOP + ZGZT group and PMOP + E2 group. The changes of mechanical pain threshold of rats were detected by von Frey filaments, and the changes of mechanical pain threshold of rats in each group were compared. Computed tomography (CT) and dual-energy X-ray were used to measure the bone mineral density of lumbar bone tissue. Enzyme-linked immunosorbent assay (ELISA) and tartrate-resistant acid phosphatase (TRAP) staining were used to detect inflammatory factors and bone metabolism related indicators. Hematoxylin-eosin (HE) staining was used to observe the tissue morphology of lumbar vertebra tissue. Western blot (WB) and quantitative polymerase chain reaction (qPCR) were used to detect AMPK/mTOR pathway- and autophagy-related factor expression. Results: ZGZT can effectively restore the bone mineral density (BMD) of PMOP rats, improve the microstructure of lumbar vertebra of PMOP rats, restore the balance of bone metabolism, promote the expression of AMPK and autophagy related factors, inhibit the expression of mTOR and the release of inflammatory factors, and increase the mechanical pain threshold of PMOP rats, so as to effectively improve osteoporosis and relieving osteoporosis pain in PMOP rats. Conclusions: ZGZT affects autophagy by regulating AMPK/mTOR pathway, restores the homeostasis of bone metabolism and inhibits the release of inflammatory factors. Moreover, the regulation of feedback pathways between bone metabolism and inflammatory factors finally plays the role of "bone strengthening" and "pain relieving". ZGZT may be a new treatment for PMOP and relieving osteoporotic pain.

Hsa_circ_0102485 inhibits the growth of cancer cells by regulating the miR-188-3p/ARID5B/AR axis in prostate carcinoma.

BACKGROUND: Studies have shown that circular RNAs (circRNAs) have significant potential as novel molecular markers for the diagnosis, treatment, and prognosis of prostate carcinoma (PCa). However, the role and mechanism of circRNA hsa_circ_0102485 in PCa remains unclear. MATERIALS & METHODS: The real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify hsa_circ_0102485 expression in PCa. The potential mechanisms and roles of hsa_circ_0102485 in tumor growth were explored using dual-luciferase-reporter and subcutaneous-xenograft assays, rescue experiments, and immunohistochemical staining. Clinical correlations were assessed by tissue-on-a-chip in-situ hybridization and Fisher's exact test. RESULTS: Hsa_circ_0102485 expression was decreased in PCa, and overexpression of hsa_circ_0102485 suppressed the proliferation, metastasis, invasion, and antiapoptotic abilities of PCa cells. MicroRNA 188-3p (MiR-188-3p) is a direct target of hsa_circ_0102485, and cotransfection of hsa_circ_0102485 in PCa cells overexpressing miR-188-3p inhibited its promotive effects. Hsa_circ_0102485 indirectly promotes the expression of AT-rich interaction domain 5B (ARID5B) and androgen receptor (AR) by sponging miR-188-3p and inhibiting PCa cell growth. Correlation analysis showed that hsa_circ_0102485 expression in PCa was not significantly correlated with the age, International Society of Urologic Pathologists (ISUP) grade, Gleason score, or lymph node metastasis status of PCa patients. CONCLUSION: Hsa_circ_0102485 plays an inhibitory role in PCa by regulating the Mir-188-3p/ARID5B/AR axis and may be a potential diagnostic biomarker and therapeutic target for PCa that requires further study.