AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via BadSer136 phosphorylation.

Epithelial disruption is the initiation of most infectious disease. Regulation of epithelium apoptosis may play a key role in balance the survival competition between resident bacteria and host cells. The role of the mTOR/p70S6K pathway in preventing apoptosis of human gingival epithelial cells (hGECs) infected with Porphyromonas gingivalis (Pg) was investigated in order to further understand the survival strategy of the epithelial cells in during Pg infecting. hGECs was challenged with Pg for 4, 12, and 24 h. Additionally, hGECs was pretreated with LY294002 (PI3K signaling inhibitor) or Compound C (AMPK inhibitor) for 12 h and exposed them to Pg for 24 h. Subsequently, apoptosis was detected using flow cytometry, and expression and activity of Bcl-2, Bad, Bax, PI3K, AKT, AMPK, mTOR, and p70S6K proteins were analyzed using western blotting. Pg-infecting did not increase apoptosis of hGECs; but the expression ratio of Bad to Bcl-2 was increased after infecting. In contrast, BadSer136 phosphorylation was promoted, accompanied by a significant reduction of mTOR/p70S6K and PI3K/AKT signaling, along with the upregulation of AMPKThr172 signaling. Morrover, the PI3K inhibitor LY294002 promoted Pg-mediated reduction of mTOR/p70S6K expression, and the increase of AMPK signaling and BadSer136 phosphorylation rate, eventually decreasing apoptosis. While Compound C inhibited Pg-mediated activation of AMPK and downregulation of mTOR/p70S6K signaling, significantly reduced the BadSer136 phosphorylation rate, thereby increasing apoptosis. Thus, hGECs prevent apoptosis via an inherent cellular-homeostasis, pro-survival mechanism during Pg infection, the AMPK/mTOR/p70S6K pathway helps prevent apoptosis in hGECs infected with Pg by regulating BadSer136 phosphorylation.

Six-year follow-up outcomes of the P(LLA-CL)/Fg bio-patch for anterior vaginal wall prolapse treatment.

INTRODUCTION AND HYPOTHESIS: There were few data about the long-term outcomes of bio-compatible patches for pelvic organ prolapse (POP). The efficacy of poly (L-lactide-co-caprolactone) blended with fibrinogen [P(LLA-CL)/Fg] bio-patches were investigated for anterior vaginal wall prolapse treatment in a 6-year follow-up. METHODS: The P(LLA-CL)/Fg bio-patch was fabricated through electrospinning. Nineteen patients with symptomatic anterior prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥ 2) were treated with anterior pelvic reconstruction surgery using a P(LLA-CL)/Fg bio-patch and were followed up at 1, 2, 3, 6 months, and 6 years. The primary outcome was objective anatomical cure (anterior POP-Q stage ≤ 1). Secondary outcomes included complications, MRI evaluation, and scores of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory-20 (PFDI-20). RESULTS: The micro-morphology of the bio-patch resembled the extracellular matrix, which was suitable for the growth of fibroblasts. Sixteen (84.2%) patients were finally assessed, with a mean follow-up of 6.08 ± 0.18 years. The cure rate without anterior prolapse recurrence was 93.8% at 6 years. Compared with baseline, the POP-Q measurements of Aa, Ba, and C points and scores of PFIQ-7 and PFDI-20 manifested significant differences at all times (all p < 0.05). One (5.26%) case of bio-patch-related infection, 1 (5.26%) case of urinary retention, and no exposures and erosion occurred. MRI evaluation showed that the bio-patch gradually degraded to fragments at 1 month and was completely absorbed at 3 months. CONCLUSIONS: Among long-term follow-ups, anterior pelvic reconstruction surgery with a P(LLA-CL)/Fg bio-patch demonstrated significant improvements in anatomical correction of anterior pelvic prolapse and pelvic function without severe morbidity.

miR-148a-3p regulates proliferation and apoptosis of idiopathic gingival fibroma by targeting NPTX1.

OBJECTIVE: Idiopathic gingival fibromatosis (IGF) is a rare heterogeneous disease that results in the progressive and diffuse hyperplasia of gingival tissues. MicroRNAs are implicated in the development and progression of various tumors. The present study aimed to explore the potential roles and mechanisms of miR-148a-3p in IGF. METHODS: Gingival fibroblasts (GFs) were transfected with miR-148a-3p mimics, miR-148a-3p inhibitors, or siNPTX1, and then, the proliferation and apoptosis of GFs and the expression of related genes were evaluated using Cell Counting Kit-8 assays, 5-ethynyl-2'-deoxyuridine assays, flow cytometry, reverse transcription-quantitative polymerase chain reaction, and western blot analysis, respectively. RESULTS: miR-148a-3p was highly expressed in GFs of IGF (IGF-GFs) as compared with normal GFs (N-GFs). Overexpression of miR-148a-3p promoted the proliferation and inhibited the apoptosis of N-GFs, whereas downregulation of miR-148a-3p had the opposite effect in IGF-GFs. Knockdown of NPTX1 reversed miR-148a-3p-mediated effects in IGF-GFs. Dual-luciferase reporter assay confirmed that NPTX1 is a direct target of miR-148a-3p. CONCLUSION: These findings identify that miR-148a-3p could regulate cell proliferation and apoptosis by targeting NPTX1, providing new insights for the further study of the molecular mechanism and treatment of IGF.

The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation.

Vesicular stomatitis virus (VSV) is an archetypal member of Mononegavirales which causes important diseases in cattle, horses and pigs. The matrix protein (M) of VSV plays critical roles in the replication, assembly/budding and pathogenesis of VSV. To further investigate the role of M during viral growth, we used a two-hybrid system to screen for host factors that interact with the M protein. Here, NADH: ubiquinone oxidoreductase complex assembly factor 4 (Ndufaf4) was identified as an M-binding partner, and this interaction was confirmed by yeast cotransformation and GST pulldown assays. The globular domain of M was mapped and shown to be critical for the M-Ndufaf4 interaction. Two double mutations (E156A/H157A, D180A/E181A) in M impaired the M-Ndufaf4 interaction. Overexpression of Ndufaf4 inhibited VSV propagation, and knockdown of Ndufaf4 by short hairpin RNA (shRNA) markedly promoted VSV replication. Finally, we also demonstrate that the anti-VSV effect of Ndufaf4 is independent of activation of the type I IFN response. These results indicated that Ndufaf4 might exploit other mechanisms to affect VSV replication. In summary, we identify Ndufaf4 as a potential target for the inhibition of VSV propagation. These results provided further insight into the study of VSV pathogenesis.

Landscape of long non-coding RNAs in Trichophyton mentagrophytes-induced rabbit dermatophytosis lesional skin and normal skin.

Emerging evidences suggest that long non-coding RNAs (lncRNAs) play important role in disease development. However, the role of rabbit lncRNAs in the pathogenesis of dermatophytosis remains elusive. The present study aimed to study and characterize lncRNA transcriptome in 8 T. mentagrophytes-induced female rabbit dermatophytosis lesional (TM) and 4 normal saline-infected (NS) skin biopsies using RNAseq. We identified 5883 lncRNAs in 12 strand-specific RNA-seq libraries and found 64 differentially expressed lncRNAs (q < 0.05) in TM relative to NS. As in other mammalian counterparts, rabbit lncRNAs were distributed in all chromosomes except the Y chromosome and were generally smaller in size and fewer in exon numbers compared to protein coding genes. Next, co-expression analysis revealed that 107 pairs between 32 DE lncRNAs and 96 protein coding genes showed a highly correlated expression (|r| > 0.8). Moreover, miRPara analysis of the lncRNAs revealed 173 lncRNAs with precursor sequences for 9561 probable novel miRNAs. Finally, q-PCR results validated the RNA-seq results with eight randomly selected lncRNAs. To the best of our knowledge, this is the first report on rabbit lncRNAs, and our results highlighted the potential role of lncRNAs in the pathogenesis of dermatophytosis.

In vivo study of novelly formulated porcine-derived fibrinogen as an efficient sealant.

Fibrinogen has been used as surgical sealant in the clinical setting for decades. The application of human plasma-derived fibrinogen is limited due to high cost and the risk of prion and virus infection. We developed a novel arginine-formulated fibrinogen from cryoprecipitates of porcine plasma. This porcine-derived fibrinogen exhibited excellent stability during sterilization and better hemostatic efficacy than a leading commercial hemostatic product in a nonlethal hemorrhage model. Therefore, it has the potential to be more economical and readily available while having a decreased risk of human blood-borne pathogen transmission.

Leflunomide in addition to steroids improves proteinuria and renal function in adult Henoch-Schoenlein nephritis with nephrotic proteinuria.

AIM: Henoch-Schoenlein nephritis (HSPN) is a severe disease in adults and may cause renal insufficiency in a large portion of patients. But its rarity has led to lack of data. There are few controlled studies on therapy with immunosuppressants in HSPN adults. This study aims to evaluate the effect of leflunomide on HSPN adults with nephrotic proteinuria. METHODS: We retrospectively studied 65 adult patients who had biopsy-proven HSPN with nephrotic proteinuria. Twenty-seven patients (Group P) only received steroids, and 38 (Group P + L) were treated with leflunomide in addition to steroids. The clinical features, laboratory data and pathological findings of both groups were analyzed. RESULTS: The two groups were well-matched at baseline. After 24 months of treatment, urinary protein excretion of both groups decreased significantly from the baseline, and the estimated glomerular filtration rate (eGFR) was higher in Group P + L. Four patients in Group P and three in Group P + L developed to end-stage renal disease at the most recent follow-up. Group P + L showed better renal outcome than Group P. The treatment group and the degree of mesangial hypercellularity were significantly related to renal prognosis. CONCLUSION: Leflunomide combined with steroids is effective for treating adult HSPN with nephrotic proteinuria.

Nano-biomaterial Fibrinogen/P(LLA-CL) for prevention of intrauterine adhesion and restoration of fertility.

Endometrial damage resulting from surgical procedures is a significant cause of intrauterine adhesion, thin endometrium, and subsequent miscarriage and infertility. Unfortunately, there is currently no effective clinical solution to promote endometrial regeneration after severe injury. In this study, we combined fibrinogen (Fg) and P(LLA-CL) by electrostatic spinning to form a stable nano-biomaterial Fg/P(LLA-CL), which can promote endometrial regeneration. After inducing physical injury to rat endometrium, we found that Fg/P(LLA-CL) membranes placed in the uterine cavities increased endometrial thickness and the number of glands after injury, while reducing the area of endometrial fibrosis. In addition, Fg/P(LLA-CL) increased neovascularization and decreased COL1A1 deposition. The expression of TGF-ß1, a cytokine that promotes fibrosis, was down-regulated in the early stage of injury. Finally, fertility assays confirmed that Fg/P(LLA-CL) improved the pregnancy rate in rats with endometrial injury, and its safety was verified by blood tests and pathological examination of heart, liver, spleen, lung, and kidney. Therefore, Fg/P(LLA-CL) shows great potential as a safe and nontoxic biomaterial for endometrial regeneration, ultimately improving pregnancy outcomes in patients with intrauterine adhesion.

Yunnan Baiyao Inhibits Periodontitis by Suppressing the Autophagic Flux.

BACKGROUND: Yunnan Baiyao (YNBY), a traditional Chinese medicine, is renowned for its anti-inflammatory properties. Recent studies have suggested that YNBY plays a significant role in inhibiting osteoclast differentiation and autophagy, which are essential processes in inflammation and bone resorption associated with periodontitis. However, the precise relationship between autophagy and the mechanism by which YNBY inhibits osteoclastogenesis remains unexplored.The primary objective of this study was to investigate the inhibitory effects of YNBY on the process of osteoclastogenesis and its potential in preventing inflammatory bone loss. METHODS: The animals were subjected to sacrifice at intervals of 2, 4, and 6 weeks postintervention whilst under deep anaesthesia, and specimens were subsequently collected. The specimens were subjected to hematoxylin and eosin (HE) staining, in addition to tartrate-resistant acid phosphatase (TRAP) staining and subsequently imaged employing a digital scanner. The confirmation of osteoclast (OC) differentiation and autophagic flux was achieved through various techniques, including western blotting, transmission electron microscopy (TEM), TRAP staining, pit formation assay, and immunofluorescence. RESULTS: The microcomputed tomography images provided evidence of the effective inhibition of alveolar bone absorption at 2, 4, and 6 weeks following YNBY treatment. Additionally, the histomorphometric evaluations of tissue segments stained with HE and TRAP, which involved measuring the distance between the alveolar bone crest (ABC) and cementoenamel junction (CEJ) and quantifying TRAP-positive OCs, yielded comparable results to those obtained through computed tomography analysis. YNBY treatment resulted in a decrease in the CEJ-ABC distance and inhibition of OC differentiation. Furthermore, in vitro studies showed that the autophagy modulators rapamycin (RAP) and 3-methyladenine (3-MA) significantly affected OC differentiation and function. YNBY attenuated the impact of RAP on the differentiation of OCs, autophagy-related factor activation, and bone resorption. CONCLUSIONS: We hypothesise that YNBY suppresses the differentiation of OC and bone resorption by blocking autophagy. This study reveals that targeting autophagy might be a new alternative treatment methodology for periodontitis treatment.

Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a crucial public health problem, accounting for approximately 2% of all cancers globally and 90% of oral malignancies over the world. Unfortunately, despite the achievements in surgery, radiotherapy, and chemotherapy techniques over the past decades, OSCC patients still low 5-year survival rate. Cisplatin, a platinum-containing drug, serves as one of the first-line chemotherapeutic agents of OSCC. However, the resistance to cisplatin significantly limits the clinical practice and is a crucial factor in tumor recurrence and metastasis after conventional treatments. Ferroptosis is an iron-based form of cell death, which is initiated by the intracellular accumulation of lipid peroxidation and reactive oxygen species (ROS). Interestingly, cisplatin-resistant OSCC cells exhibit lower level of ROS and lipid peroxidation compared to sensitive cells. The reduced ferroptosis in cisplatin resistance cells indicates the potential relationship between cisplatin resistance and ferroptosis, which is proved by recent studies showing that in colorectal cancer cells. However, the modulation pathway of ferroptosis reversing cisplatin resistance in OSCC cells still remains unclear. This article aims to concisely summarize the molecular mechanisms and evaluate the relationship between ferroptosis and cisplatin resistance OSCC cells, thereby providing novel strategies for overcoming cisplatin resistance and developing new therapeutic approaches.

Yunnan Baiyao Might Mitigate Periodontitis Bone Destruction by Inhibiting Autophagy and Promoting Osteoblast Differentiation in vivo, ex vivo and in vitro.

Background and Objective: Periodontitis is an inflammatory disease that eventually destroys tooth-supporting tissue. Yunnan Baiyao (YNBY), a traditional Chinese medicine compound with haemostatic and anti-inflammatory properties has shown therapeutic potential in several diseases. Our previous study revealed that YNBY suppressed osteoclast differentiation in periodontitis. The purpose of this study is to investigate the influences of YNBY on osteoblasts and explore its potential mechanisms. Materials and Methods: A rat periodontitis model was established by ligation of maxillary second molars. After the end of modelling, histopathological observation by hematoxylin-eosin (HE) staining and Masson trichrome staining, detection of bone resorption by Micro-CT scanning, detection of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining, expression of osteocalcin (OCN) and microtubule-associated protein 1 light chain 3 (LC3) by immunohistochemistry. Lipopolysaccharides was used to irritate MC3T3-E1 osteoblastic cells and ex vivo calvarial organ as an in vitro model of inflammation. CCK-8 assay was performed to examine the toxicity of YNBY to MC3T3-E1 osteoblastic cells. Osteogenesis was assessed with alizarin red staining, immunofluorescence staining, Western blot and immunohistochemical staining. Transmission electron microscopy, fluorescent double staining, Western blot and immunohistochemical staining were employed to detect autophagy. Results: Histological and micro-CT analyses revealed that YNBY gavage reduced bone loss caused by experimental periodontitis and upregulated osteogenic proteins in vivo. YNBY attenuated the production of autophagy-related proteins in periodontitis rats. Additionally, YNBY promoted osteogenesis by inhibiting inflammation-induced autophagy in vitro. Furthermore, YNBY suppressed LPS-mediated bone resorption and promoted the production of osteoblast-related proteins in inflamed calvarial tissues ex vivo. Conclusion: This study demonstrated, through in vivo, in vitro and ex vivo experiments, that YNBY promoted osteoblast differentiation by suppressing autophagy, which markedly alleviated bone destruction caused by periodontitis.

Quercetin through miR-147-5p/Clip3 axis reducing Th17 cell differentiation to alleviate periodontitis.

Background: Quercetin (QU) plays an important role in treating periodontitis; however, the mechanism through which microRNAs regulate Th17 cell differentiation has not been determined. Methods: QU was administered intragastrically to periodontitis rats once a day for one month. The morphology of alveolar bone was observed by micro-CT, gingival tissue structure was observed by HE staining, IL-6, TNF-α, IL-17A, RORγt, FOXP3 and IL-10 were detected by immunohistochemical staining, and Th17 and Treg cells in the peripheral blood were detected by flow cytometry. CD4+T cells were induced to differentiate into Th17 cells in vitro. Cell viability was determined by CCK8, and IL-17A and RORγt were detected by qPCR. Th17 cells were detected by flow cytometry, microRNA sequencing and bioinformatics analysis were used to screen key microRNAs, the phenotypic changes of Th17 cells were observed after overexpressed microRNAs via mimics. TargetScan database, in situ hybridization, and dual-luciferase reporter experiment were used to predict and prove target genes of microRNAs. The phenotype of Th17 cells was observed after overexpression of microRNA and target gene. Results: Compared with periodontitis group, the distance from cementoenamel junction(CEJ) to alveolar bone(AB) was decreased, the structure of gingival papilla was improved, IL-6, TNF-α, IL-17, and RORγt were downregulated, FOXP3 and IL-10 were upregulated, the proportion of Th17 decreased and Treg increased in peripheral blood after QU treatment. Compared with Th17 cell group, mRNA levels of IL-17A and RORγt were decreased, and proportion of Th17 cells was significantly lower in the coculture group. MiR-147-5p was low in control group, upregulated in Th17 cell group, and downregulated after QU intervention, it's eight bases were inversely related to 3'UTR of Clip3, miR-147-5p with Clip3 were co-located in cells of periodontal tissue. Compared with those in Th17-mimicsNC + QU cells, the mRNA levels of RORγt and IL-17A upregulated, and proportion of Th17 cells increased in Th17-miR-147-5p + QU cells. The miR-147-5p mimics inhibited the luciferase activity of the WT Clip3 3'UTR but had no effect on the Mut Clip3 3'UTR. Clip3 was significantly downregulated after the overexpression of miR-147-5p. Mimics transfected with miR-147-5p reversed the decrease in the proportion of Th17 cells induced by QU, while the overexpression of Clip3 antagonized the effect of miR-147-5p and further reduced the proportion of Th17 cells. Moreover, the overexpression of miR-147-5p reversed the decreases in the mRNA levels of IL-17 and RORγt induced by QU treatment, while pcDNA3.1 Clip3 treatment further decreased the mRNA levels of IL-17 and RORγt. Conclusion: QU reducing inflammatory response and promoting alveolar bone injury and repair, which closely relative to inhibit the differentiation of CD4+T cells into Th17 cells by downregulating miR-147-5p to promote the activation of Clip3.

Effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen for diabetic foot ulcers.

Diabetic foot ulcers were a significant complication of diabetes and were accompanied by delayed wound healing. To compare the effect of topical application electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing with alginate dressing when treating diabetic foot ulcers (DFUs). A single-center, prospective, randomized, patient-blinded clinical trial was conducted from July 1, 2023, to December 26, 2023. The clinical trial registration was completed on August 28, 2023 (ClinicalTrials.gov Identifier: NCT06014437). The eligible patients with DFUs of 1-20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or alginate dressing. Participants received PLCL/Fg dressing 1-3 times per week or alginate dressing 3 times per week for 12 weeks. A total of 52 patients (33 men [63.5 %]; mean [SD] age, 63.1 [11.9] years; mean [SD] diabetes time, 8.3 [4.6] years) with DFUs were assessed for this study. The DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 3.8 [3.2] cm2) were randomized to receive either the PLCL/Fg dressing (n = 26) or the alginate dressing (n = 26) for as long as 12 weeks. In this study, the incidence of complete healing included 22 patients (91.7 %) in the PLCL/Fg group and 14 (63.6 %) in the alginate group during the 12-week treatment period (P = 0.003). The treatment-related adverse events that occurred were 5 (20.8 %) in the PLCL/Fg group and 4 (18.1 %) in the comparator group. In this randomized clinical trial, PLCL/Fg dressing showed beneficial effects in DFUs treatment of wound surface reduction and regulating the wound microenvironment.

Screening parameters for diagnosing primary aldosteronism in patients with moderate to severe obstructive sleep apnea hypopnea syndrome and resistant hypertension.

Background: Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH. Methods: Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated. Results: A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value. Conclusion: ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment.

Apoptosis of periodontium cells in streptozototocin- and ligature-induced experimental diabetic periodontitis in rats.

OBJECTIVE: The aim of this study was to investigate the presence of apoptosis of periodontium cells in streptozototocin- and ligature-induced experimental diabetic periodontitis in rats. MATERIALS AND METHODS: Sixty-two 6-week-old male Sprague-Dawley (SD) rats were randomly divided into three groups: the diabetic periodontitis group (group DP; n = 22), periodontitis group (group P; n = 20) and normal control group (group N; n = 20). Diabetes was induced by intraperitoneal injection of streptozototocin (STZ). Periodontitis was initiated by ligating floss around maxillary second molars. The animals were sacrificed at 3 and 6 weeks after ligature placement in the P and DP groups. Maxillary dentoalveolar segments were isolated and were prepared for morphometric analysis of alveolar bone loss (ABL) and for histological analysis. RESULTS: ABL was significantly increased in group DP compared with group P (p < 0.05). The number of PDL fibroblasts, osteoblasts and osteocytes in group DP was decreased compared with group P (p < 0.05). Inter-group analysis revealed higher osteoclast numbers in the inflammatory area of group DP and group P when compared with group N (p < 0.05). Also, compared with group P, group DP had more higher osteoclast numbers (p < 0.05). Periodontitis and diabetic periodontitis also increased apoptosis of fibroblasts, osteoblasts and osteocytes. The percentage of these apoptotic cells was ∼ 2-fold higher in group DP vs group P. CONCLUSIONS: The results of these studies suggest that diabetes may have a negative effect on the periodontium by increasing the formation of osteoclasts and enhancing apoptosis of fibroblasts, osteoblasts and osteocytes in the periodontal tissue.

Fibrinogen/poly(l-lactide-co-caprolactone) copolymer scaffold: A potent adhesive material for urethral tissue regeneration in urethral injury treatment.

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The in vitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The in vivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen-PLCL scaffold is more appropriate for urethral defect reconstruction.

Preclinical animal study of electrospun poly (l-lactide-co-caprolactone) and formulated porcine fibrinogen for full-thickness diabetic wound regeneration.

Diabetic foot ulcer is one of the most serious chronic complications of diabetes mellitus. It may lead to amputation of the lower extremities for diabetics. Our study was to evaluate the effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) wound dressing on animal wound model. A blend ratio of PLCL/Fg scaffold was 4 (PLCL):1 (Fg). The scanning electron microscopy findings showed that the fibers' diameter was 122.5 ± 80.3 nm, and the tensile strength was 9.2 ± 0.2 MPa. In-vivo study of the hog normal model demonstrated that PLCL/Fg dressing had better biocompatibility, degradability, and ability to restore the skin's normal structure. We evaluated the wound healing processes in the rat diabetic model by macroscopic observation and histological observation at 1, 2, and 3 post-operation weeks. In our study, the PLCL/Fg group performed better 3 weeks after surgery, in terms of macroscopic healing and scarring. After surgery, the PLCL/Fg group showed better fibroblast accumulation, tissue granulation, and collagen expression than the control group. Topical treatment with PLCL/Fg dressing effectively enhanced wound healing in both normal and hyperglycemic conditions, suggesting that it may possess wound-healing potential.

Renal venous sampling assisted the diagnosis of juxtaglomerular cell tumor: a case report and literature review.

Juxtaglomerular cell tumor (JCT) is an endocrine tumor marked by elevated renin levels and high blood pressure. This case report presents the clinical findings of a 47-year-old woman with a history of recurrent hypokalemia, headaches, hypertension, and increased plasma renin activity (PRA). Dynamic enhanced magnetic resonance imaging (MRI) revealed a small nodule on the upper part of the right kidney. Selective renal venous sampling indicated a higher PRA only in the right upper pole renal vein. The patient underwent surgical removal of the right kidney mass, and the pathology results confirmed the diagnosis of JCT. This case underscores the importance of conducting selective renal venous sampling for accurate JCT diagnosis.

Yunnan Baiyao Ameliorates Rheumatoid Arthritis in Rats by Shifting the Th17/Treg Cell Balance and Preventing Osteoclast Differentiation.

Yunnan Baiyao (YNB) is a traditional Chinese medicine that possesses anti-inflammatory effects. Previously, we have demonstrated the effects of YNB in rheumatoid arthritis (RA) animal models; however, the underlying mechanisms are unclear. In the present study, we aimed to investigate the effects of YNB on the T-helper (Th)17/T-regulatory (Treg) cell balance in a collagen-induced arthritis rat model orally administrated YNB or methotrexate, a widely used therapeutic agent for treating RA. Our results showed that YNB treatment significantly decreased the voix pedis thickness and joint functionality scores and alleviated joint histopathology in these rats. These YNB-induced effects were achieved by decreasing the number of Th17 cells and increasing that of Treg cells in the spleen. Moreover, the interleukin- (IL-) 17 level considerably decreased in the serum of YNB-treated rats, whereas the IL-10 level significantly increased. Furthermore, YNB could inhibit RANKL-induced osteoclast formation by regulating the tumor necrosis factor receptor-associated factor 6/NF-κB/nuclear factor of the activated T-cell pathway. In summary, our study shows that YNB exhibits antiarthritic activity by decreasing the ratio of Th17/Treg cells, regulating the cytokine balance, and inhibiting osteoclast activation, providing an experimental basis that supports the use of this traditional Chinese medicine for the clinical treatment of RA.