Prognosis and therapeutic significance of IGF-1R-related signaling pathway gene signature in glioma.

Background: Glioma is the most common cancer of the central nervous system with poor therapeutic response and clinical prognosis. Insulin-like growth factor 1 receptor (IGF-1R) signaling is implicated in tumor development and progression and induces apoptosis of cancer cells following functional inhibition. However, the relationship between the IGF-1R-related signaling pathway genes and glioma prognosis or immunotherapy/chemotherapy is poorly understood. Methods: LASSO-Cox regression was employed to develop a 16-gene risk signature in the TCGA-GBMLGG cohort, and all patients with glioma were divided into low-risk and high-risk subgroups. The relationships between the risk signature and the tumor immune microenvironment (TIME), immunotherapy response, and chemotherapy response were then analyzed. Immunohistochemistry was used to evaluate the HSP90B1 level in clinical glioma tissue. Results: The gene risk signature yielded superior predictive efficacy in prognosis (5-year area under the curve: 0.875) and can therefore serve as an independent prognostic indicator in patients with glioma. The high-risk subgroup exhibited abundant immune infltration and elevated immune checkpoint gene expression within the TIME. Subsequent analysis revealed that patients in the high-risk subgroup benefited more from chemotherapy. Immunohistochemical analysis confirmed that HSP90B1 was overexpressed in glioma, with significantly higher levels observed in glioblastoma than in astrocytoma or oligodendrocytoma. Conclusion: The newly identified 16-gene risk signature demonstrates a robust predictive capacity for glioma prognosis and plays a pivotal role in the TIME, thereby offering valuable insights for the exploration of novel biomarkers and targeted therapeutics.

Flowering Ocimum gratissimum intercropped in tea plantations attracts and reduces Apolygus lucorum populations.

BACKGROUND: Apolygus lucorum is one of the most important piercing-sucking insect pests of the tea plant In this study, we assessed the attractiveness of basil plants to A. lucorum and the effectiveness of Ocimum gratissimum L. in the control of A. lucorum. The control efficiency of main volatile chemicals emitted from O. gratissimum flowers was also evaluated. RESULTS: Among seven basil varieties, O. gratissimum was more attractive to A. lucorum adults and was selected as a trap plant to assess its attractiveness to A. lucorum and effects on natural enemies in tea plantations. The population density of A. lucorum on trap strips of O. gratissimum in tea plantations was significantly higher than that on tea at 10-20 m away from the trap strips. Intercropping O. gratissimum with tea plants, at high-density significantly reduced A. lucorum population levels. Eucalyptol, limonene, ß-ocimene, and linalool were the four dominant components in the O. gratissimum flower volatiles, and their emissions showed a gradual upward trend over the sampling period. Olfactometer assays indicated that eucalyptol and dodecane showed attraction to A. lucorum. High numbers of A. lucorum were recorded on limonene, eucalyptol, and myrcene-baited yellow sticky traps in field trials in which 11 dominant volatiles emitted by O. gratissimum flowers were evaluated. CONCLUSION: Our research indicated that the aromatic plant O. gratissimum and its volatiles could attract A. lucorum and planting O. gratissimum has the potential as a pest biocontrol method to manipulate A. lucorum populations in tea plantations. © 2024 Society of Chemical Industry.

A comparison of interferential current efficacy in elderly intervertebral disc degeneration patients with or without sarcopenia: a retrospective study.

BACKGROUND: Intervertebral disc degeneration and sarcopenia are both age-related diseases without effective treatments. Their comorbidities may worsen the prognosis, and further studies on interaction and therapy are needed. The purpose of the study was to investigate the prevalence of sarcopenia in intervertebral disc degeneration, and to compare the characteristics of intervertebral disc degeneration with and without sarcopenia and effects of interferential current. METHODS: One hundred twenty disc degeneration patients were included from 2021 to 2022 in a single institute. Medical records, examination results and radiological reports were reviewed. Patients with sarcopenia were screened and grouped according to Asian Working Group for Sarcopenia 2019. VAS, ODI, SARC-F, SMI, gait speed (GS), grip strength, disc Pfirrmann grading, standard cross-sectional area (SCSA), degree of fatty infiltration (DFF), and nerve conduction velocity (NCV) were assessed before and after treatment. RESULTS: The prevalence of sarcopenia in intervertebral disc degeneration was 28.3%. The difference of VAS, ODI, disc Pfirrmann grading, SCSA, DFF and NCV between two groups were significant before intervention (P < 0.05), SCSA and DFF were related to the degree of disc degeneration. The improvement of SMI, GS, grip strength, VAS, SARC-F and ODI in intervertebral disc degeneration with sarcopenia group was significant after intervention, as well as SMI, GS, grip strength, VAS and ODI in those without sarcopenia (P < 0.05). The improvement of grip strength, GS, ODI and SARC-F in intervertebral disc degeneration with sarcopenia group were greater than the one without sarcopenia (P < 0.05), whereas there was no significance in improvement degree of other indicators between the two groups (P > 0.05). CONCLUSION: The prevalence of sarcopenia was high in intervertebral disc degeneration, and paravertebral muscles degeneration correlated with the degree of disc degeneration. Compared to those without sarcopenia, intervertebral disc degeneration patients with sarcopenia have more severe pain, poorer mobility and neurological function. Interferential current is effective in intervertebral disc degeneration patients and sarcopenia patients.

Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers. METHODS: We used two-sample Mendelian randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR-Egger regression and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods. All the results were examined by false discovery rate (FDR) with the Benjamin and Hochberg method for this correction to minimize false positives. We used R language for the analysis. RESULTS: All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (odds ratio [OR] = 0.639, 95% confidence interval [CI]: 0.435-0.938) and IL-1R1 (OR = 0.603, 95% CI = 0.417-0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 and increased C-C motif chemokine 3. Hospitalized COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had higher mean platelet volume (MPV) and lower platelet count. These changes in TFPI, tPA, IL-1R1, MPV, and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis. CONCLUSION: TFPI, IL-1R, and seven other indicators provide causal clues of the pathogenesis of COVID-19 and thrombosis. This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level.

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

Myth or fact: 3D-printed off-the-shelf prosthesis is superior to titanium mesh cage in anterior cervical corpectomy and fusion?

BACKGROUND: To find out if three-dimensional printing (3DP) off-the-shelf (OTS) prosthesis is superior to titanium mesh cages in anterior cervical corpectomy and fusion (ACCF) when treating single-segment degenerative cervical spondylotic myelopathy (DCSM). METHODS: DCSM patients underwent ACCF from January 2016 to January 2019 in a single center were included. Patients were divided into the 3DP group (28) and the TMC group (23). The hospital stays, operation time, intraoperative blood loss, and the cost of hospitalization were compared. The Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI) were recorded pre-operatively, 1 day, 3, 6, 12, and 24 months post-operatively. Radiological data was measured to evaluate fusion, subsidence, and cervical lordosis. Patients were sent with SF-36 to assess their health-related quality of life (HRQoL). RESULTS: The differences in operative time, intraoperative blood loss, and hospital stay were not statistically significant between groups (p > 0.05). Postoperative dysphagia occurred in 2 cases in the 3DP group and 3 cases in the TMC group, which all relieved one week later. The difference in improvement of JOA and NDI between the two groups was not statistically significant (p > 0.05). No hardware failure was found and bony fusion was achieved in all cases except one in the 3DP group. The difference in cervical lordosis (CL), fused segmental angle (FSA), mean vertebral height (MVH), and subsidence rates between groups at each follow-up time point was not statistically significant and the results of the SF-36 were similar (p > 0.05). The total cost was higher in the 3DP group with its higher graft cost (p < 0.05). CONCLUSION: In treating single-segment DCSM with ACCF, both 3DP OTS prosthesis and TMC achieved satisfactory outcomes. However, the more costly 3DP OTS prosthesis was not able to reduce subsidence as it claimed.

Risk factors of instrumentation failure after laminectomy and posterior cervical fusions (PCF).

BACKGROUND: For patients with multilevel degenerative cervical myelopathy, laminectomy and posterior cervical fusions (PCF) with instrumentation are widely accepted techniques for symptom relief. However, hardware failure is not rare and results in neck pain or even permanent neurological lesions. There are no in-depth studies of hardware-related complications following laminectomy and PCF with instrumentation. METHODS: The present study was a retrospective, single centre, observational study. Patients who underwent laminectomy and PCF with instrumentation in a single institution between January 2019 and January 2021 were included. Patients were divided into hardware failure and no hardware failure group according to whether there was a hardware failure. Data, including sex, age, screw density, end vertebra (C7 or T1), cervical sagittal alignment parameters (C2-C7 cervical lordosis, C2-C7 sagittal vertical axis, T1 slope, Cervical lordosis correction), regional Hounsfield units (HU) of the screw trajectory and osteoporosis status, were collected and compared between the two groups. RESULTS: We analysed the clinical data of 56 patients in total. The mean overall follow-up duration was 20.6 months (range, 12-30 months). Patients were divided into the hardware failure group (n = 14) and no hardware failure group (n = 42). There were no significant differences in the general information (age, sex, follow-up period) of patients between the two groups. The differences in fusion rate, fixation levels, and screw density between the two groups were not statistically significant (p > 0.05). The failure rate of fixation ending at T1 was lower than that at C7 (9% vs. 36.3%) (p = 0.019). The regional HU values of the pedicle screw (PS) and lateral mass screw (LMS) in the failure group were lower than those in the no failure group (PS: 267 ± 45 vs. 368 ± 43, p = 0.001; LMS: 308 ± 53 vs. 412 ± 41, p = 0.001). The sagittal alignment parameters did not show significant differences between the two groups before surgery or at the final follow-up (p > 0.05). The hardware failure rate in patients without osteoporosis was lower than that in patients with osteoporosis (14.3% vs. 57.1%) (p = 0.001). CONCLUSIONS: Osteoporosis, fixation ending at C7, and low regional HU value of the screw trajectory were the independent risk factors of hardware failure after laminectomy and PCF. Future studies should illuminate if preventive measures targeting these factors can help reduce hardware failure and identified more risk factors, and perform long-term follow-up.

Transmitter dispersion eye closure quaternary assessment based on linear CNN with 1 × 1 convolutional kernel.

Transmitter dispersion eye closure quaternary (TDECQ) is a vital metric to characterize the quality of four-level pulse amplitude modulation (PAM-4) optical signals. However, the traditional TDECQ assessment scheme is complex and time consuming, with heavy iterative operations. Therefore, accelerating the TDECQ assessment has great significance for photonic data-center interconnection (DCI) applications. Here, we propose and experimentally demonstrate a TDECQ assessment based on linear-convolutional neural network (L-CNN) with the 1 × 1 convolutional kernel to reduce the implementation complexity. Our experimental results verify that the lightweight L-CNN can realize the accurate TDECQ assessment, without the involvement of nonlinear activation functions (NAFs). The mean absolute error (MAE) of 26.5625 and 53.125 GBaud PAM-4 signals are 0.16 dB and 0.18 dB, respectively, over a TDECQ range from 1.5 to 4.0 dB. Meanwhile, in comparison with existing CNN-based schemes, the L-CNN based TDECQ assessment scheme only needs 2048 multiplications, which have been reduced by five orders of magnitude.

Myoblast-derived exosomal Prrx2 attenuates osteoporosis via transcriptional regulation of lncRNA-MIR22HG to activate Hippo pathway.

BACKGROUND: Sarcopenia and osteoporosis are common diseases that predominantly affect older individuals. The interaction between muscle and skeleton exerts pivotal roles in bone remodeling. This study aimed to explore the function of myoblast-derived exosomal Prrx2 in osteogenic differentiation and its potential mechanisms. METHODS: Exosomes were isolated from myogenic differentiated C2C12 cells. qRT-PCR and Western blotting were used to determine target molecule expression. Osteogenic differentiation of BMSCs was evaluated by Alizarin red staining, ALP activity and levels of OCN, OPN, RUNX2, and BMP2. Dual-luciferase reporter assay, RIP, and ChIP assays were performed to verify the interaction between molecules. The nuclear translocation of YAP1 was observed by immunofluorescence staining. In vivo osteoporotic model was established by ovariectomy in mice. Bone loss was examined using HE staining. RESULTS: Prrx2 expression was elevated in myogenic differentiated C2C12 cells and their exosomes. Myoblast-derived exosomal Prrx2 enhanced osteogenic differentiation of BMSCs. Delivering exosomal Prrx2 directly bond to MIR22HG promoter and promoted its transcription and expression. MIR22HG enhanced expression and nuclear translocation of YAP via sponging miR-128, thus facilitating BMSC osteogenic differentiation. Knockdown of exosomal Prrx2 suppressed osteogenic differentiation, which could be abolished by MIR22HG overexpression. Similarly, miR-128 inhibitor or YAP overexpression reversed the inhibitory effect of MIR22HG depletion or miR-128 mimics on osteogenic differentiation. Finally, myoblast-derived exosomal Prrx2 alleviated osteoporosis in mice via up-regulating MIR22HG and activating the Hippo pathway. CONCLUSION: Myoblast-derived exosomal Prrx2 contributes to transcriptional activation of MIR22HG to activate YAP pathway via sponging miR-128, thereby facilitating osteogenic differentiation of BMSCs.

The antifibrotic and anti-inflammatory effects of FZHY prescription on the kidney in rats after unilateral ureteral obstruction.

PURPOSE: To explore the potential impact of traditional Chinese herb FuZhengHuaYuJiangZhuTongLuo recipe (FZHY) on renal interstitial fibrosis (RIF) in chronic kidney disease (CKD) at cellular and molecular levels. METHODS: Unilateral ureteral obstruction (UUO) rats were established as the RIF model in vivo. The rats were given intragastric administration with FZHY once a day for consecutive 7, 14 and 21 days, respectively. The renal function parameters and inflammation indicators in kidney tissues were measured using enzyme-linked immunosorbent assay, the CD4+/CD8+ T cells in peripheral blood was detected using flow cytometry, the renal fibrosis degree was estimated using Masson's staining, and the fibrosis-related genes' expression was detected using quantitative polymerase chain reaction, western blotting, and immunohistochemistry analyses. RESULTS: FZHY prescription reduced the serum creatinine and blood urea nitrogen, decreased the levels of c-reactive protein, interleukin-1, interleukin-6 and tumor necrosis factor-α in kidney tissues, and increased the ratio of CD4+/CD8+ T cells in peripheral blood. FZHY prescription suppressed the renal tissue fibrosis and reduced the levels of laminin, fibronectin, collagen I and collagen III. CONCLUSIONS: FZHY prescription suppressed the renal fibrosis and improved the condition of "Healthy Qi Deficiency and Evil Qi Excess" in rats with UUO, which may provide an effective method for CKD treatment.

Is 3D-printed prosthesis stable and economic enough for anterior spinal column reconstruction after spinal tumor resection? A retrospective comparative study between 3D-printed off-the-shelf prosthesis and titanium mesh cage.

OBJECT: To investigate the stability and cost-effectiveness of the three-dimensional-printed (3DP) off-the-shelf (OTS) prosthesis in the reconstruction of the anterior column of the thoracic/lumbar spine after tumor resection. METHODS: Thirty-five patients (26 with primary malignant tumors and nine with metastatic malignant tumors) who underwent tumor resection and anterior column reconstruction between January 2014 and January 2019 were included in a single institute. Patients were divided into the 3DP OTS prosthesis (3DP) group (n = 14) and the titanium mesh cage (TMC) group (n = 21) by the type of implant. The operation time, intraoperative blood loss, hospital stay, history of radiotherapy, surgical level and total cost were collected and compared between the two groups. Mechanical complications and radiological parameters including mean vertebral height, subsidence, fixation failure(nonunion, migration, screw loosening, rod breakage) rate were recorded at preoperation, 1 week, 3 months, 6 months, 12 months after surgery then at 1 year interval or stop until the end of survival. The follow-up patients were also sent with short form-36 to assess their health-related quality of life (HRQoL) and questions about the current condition of their disease. RESULTS: The mean overall follow-up was 24.6 months. Of the 35 patients involved, six patients died and six were lost to follow-up. The differences between the two groups in operative time, intraoperative blood loss, and hospital stay were not statistically significant (p > 0.05). The differences in fixation failure and the subsidence rate between the two groups were not statistical significant (p > 0.05). The difference of subsidence rate between the cases with and without osteoporosis, cases with and without radiotherapy was statistically significant within each group (p < 0.05). However, the difference of subsidence rate between the surgical level above or below T10 was not statistically significant (p > 0.05). The response rate of the questionnaire among the survived patients was 100% (23/23 patients). The results of the Short Form- (SF-)36 between the two groups were similar (p > 0.05). The total cost was higher in the 3DP group (p < 0.05) with its higher graft cost (p < 0.05), but the differences in internal fixation cost and other cost were not statistically significant between groups (p > 0.05). CONCLUSION: Compared to TMC, the 3DP OTS prosthesis achieved similar clinical and radiological results in spinal anterior spinal column reconstruction of thoracic/lumbar spinal tumor resection. However, the 3DP OTS prosthesis was more expansive than TMC.

Exploring the Risk Factors of Conjunctival Squamous Cell Carcinoma and Establishing a Prognostic Model: Retrospective Study.

Objective: Exploring the risk factors of conjunctival squamous cell carcinoma (CSCC) and establishing a prognostic model. Methods: Information on patients with CSCC was extracted from the SEER database, conducting a retrospective study. 650 patients with CSCC were finally included in the model. Descriptive analysis was performed by Chi-square test and T-test. The risk factors of CSCC were explored by COX multivariate analysis, and the corresponding prognostic model was established as a result. Results: The all-cause mortality rate of CSCC was 38.3%, and the risk factors were age (HR = 1.077), sex (HR = 0.691), grade (HR = 7.857), laterality (HR = 1.403), N (HR = 7.195), M (HR = 0.217), and surgery (HR = 1.618), all P < 0.05. The new model had C index and area under curve ROC (AUC) value greater than 0.7. Calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement (IDI), and Decision Curve Analysis (DCA) indicate the new model has better predictive performance than the American Joint Committee on Cancer (AJCC-TNM). Conclusions: Compared with the clinical guidance of AJCC (TNM) for patients with CSCC, the established model exhibits good performance and can provide guidance for clinical decision-making.

Surgical Treatment of Bilateral Chronic Subdural Hematoma.

Background: Chronic subdural hematoma (CSDH) is one of the common clinical intracranial hemorrhagic disorders, accounting for 16%-20% of bilateral CSDH. At present, the surgical treatment of bilateral CSDH mainly includes drilling drainage and neuroendoscopic assistance. The main objective of this paper was to compare the effects of two surgical methods on CSDH. Methods: 153 patients who were diagnosed with CSDH were included in this study. 79 patients were treated with bilateral drilling drainage, and the other 74 patients were treated with neuroendoscope-assisted drainage. The clinical data of the two groups were compared, and the surgical indexes, neurological function, cure rate, and recurrence rate of the two groups were compared. The operation indexes of patients include operation time, postoperative hematoma volume, hospital stay, extubation time, misplacement of drainage tube, recurrence, and hematoma clearance rate. Results: All patients underwent CT examination one day after operation. The CT imaging detection of the two groups was generally good. The cranial CT was reexamined before discharge. The bilateral hematoma disappeared in 114 patients, the unilateral hematoma disappeared in 29 patients, a small amount of compensatory crescent very low-density shadow subdural effusion was observed on the other side, and a small amount of compensatory crescent very low-density shadow subdural effusion was observed on both sides in 10 patients. There was no space occupying effect and intracranial gas disappeared. Compared with neuroendoscopic assisted drainage, the operation time of drilling drainage patients was significantly shorter. The extubation time, drainage tube dislocation, recurrence rate, postoperative hematoma volume, and hematoma clearance rate of patients receiving neuroendoscopic assisted drainage were significantly better than those receiving drilling drainage. The Markwalder score and hospital stay between the two groups were not significant. Conclusions: Drilling drainage and neuroendoscopic assisted surgery have good therapeutic effects on bilateral CSDH. The operation time of drilling drainage is shorter. Neuroendoscopic assisted surgery has more advantages in extubation time, misplacement of drainage tube, recurrence, postoperative hematoma volume, and hematoma clearance rate.

FuZhengHuaYuJiangZhuTongLuoFang Prescription Modulates Gut Microbiota and Gut-Derived Metabolites in UUO Rats.

Background: Alteration of intestinal flora and metabolites is closely related to chronic kidney disease (CKD) across early to advanced stages. FuZhengHuaYuJiangZhuTongLuoFang prescription (FZHY) is a Chinese herb that has been proven to effectively treat CKD, but the underlying mechanism is not clear. Methods: Rats were subjected to intragastric treatment with FZHY 7, 14, and 21 days after unilateral ureteral obstruction (UUO) surgery, and kidney tissue, colon tissue, serum, and stool samples were collected. Results: FZHY treatment effectively ameliorated UUO-induced renal function loss, renal injury and renal fibrosis, and colon tissue damage and fibrosis on day 7. The results of 16S flora analysis (day 7) showed that, compared with the UUO group, both the FZHY group and the sham group showed decreased levels of g_Monoglobus, g_Papillibacter, g_Eubacterium_nodatum, and g_Family_XIII_AD3011. Additionally, FZHY obviously induced the reduction of serum citrulline, glycoursodeoxycholic acid, 23-nordeoxycholic acid, 7-ketodeoxycholic acid, kahweol, lipoid B4, 4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-2-methyl-1,3-thiazole, taurolithocholic acid sodium salt, indoline-2-carboxylic acid, 5(S),15(S)-diHETE, and others and the increase of bilirubin, asparagine, and others, which were positively associated with the above four candidate bacteria. Moreover, FZHY increased the levels of ZO-1, occludin, and claudin-1 in the colonic mucosa and reduced the levels of CRP, TNF-α, IL-6, and IL-1 in the serum and LN, FN, Col-I, and Col-III in the tubulointerstitium of UUO rats on day 7. Conclusion: Our study revealed that FZHY reduced kidney damage at the early stage of CKD by regulating the above four candidate bacteria biomarkers and gut-derived harmful metabolites, inhibiting the inflammation response and tubulointerstitial fibrosis, providing deep insight into CKD therapeutic strategy.

Mitochondrial-Targeted Antioxidant Peptide SS31 Prevents RPE Cell Death under Oxidative Stress.

This work aims at investigating the protective effects of the mitochondria-targeted peptide SS31, on mitochondria function, preventing human retinal pigment epithelial cell-19 (ARPE-19) cell apoptosis. The ARPE-19 cells were subjected to 24 h of intervention with H2O2 of various concentrations (0, 100, 150, 200, 250, 300, and 500 µmol/L). Various concentrations of SS31 (10 nM, 100 nM, and 1 µmol/L) pretreated the cells for 2 h. The MTT assay determined cell viability. ARPE-19 cell apoptosis was observed by 4',6-diamidino-2-phenylindole (DAPI) staining under fluorescence microscope and detected by Annexin-V/PI staining under flow cytometry. The measurement of reactive oxygen species (ROS) release level used MitoSOX Red (a mitochondrial superoxide indicator) and the probe 2'-7'dichlorofluorescin diacetate (DCFH-DA). And with the use of a JC-1 probe, the mitochondrial membrane potential (MMP; ΔΨm) was analyzed. Reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR were responsible for measuring the levels of apoptosis related genes (Bcl-2, Bax, and Caspase-3). The cell viability increased significantly with SS31 pretreated (P < 0.05). In the SS31 + H2O2 group, the fluorescence of the cell nuclei with DAPI staining was weaker than H2O2 along group accordance with the decreased ratio of apoptotic cells (P < 0.05). The ROS generation decreased in SS31 pretreated group, with the increased ΔΨm. The RT-PCR result showed decreased Bax gene and Caspase-3 gene expression with SS31 pretreatment, while increased antiapoptotic gene Bcl-2 (P < 0.05). We provide evidence that SS31 promotes resilience of RPE cells to oxidative stress by stabilizing mitochondrial function.

Glycyrrhizic acid assists anti-psoriatic efficacy of a self-deformable curcumin loaded transdermal gel.

The aim of this study was to explore the function of glycyrrhizic acid (GA) in an anti-psoriatic dermal delivery, whereby GA is originally designed as the matrix agent, with curcumin (Cur) as the active agent and silica as the drug carrier. Formulations with different GA proportions were prepared and named W-GA (without GA), L-GA (13% w/w GA) and H-GA (26% w/w GA). The results showed that GA had no significant effect on the physical characteristics, such as particle size and amorphous state, as exhibited by scanning electron microscopy and x-ray diffractograms, respectively. Compared with W-GA and L-GA, H-GA resulted in 10% less photodegradation of Cur after storage for one month, 0.45 µg more penetrated Cur in the epidermis, 2-fold higher viscosity, fewer signals of imiquimod-induced psoriasiform skin lesions and less histological morphological changes. The findings showed that H-GA significantly inhibited expression of interleukin 17 A in the dermis, and interleukin IL-23 in the epidermis, compared with Cur raw drug powder (RDP), whereas L-GA had no significant effect on the expression. These results indicated that a high GA proportion results in superior anti-psoriatic efficacy. Therefore, Cur-loaded silicas with approximately 26% GA are recommended as the superior formulation for the treatment of psoriasis.

SLC3A2 inhibits ferroptosis in laryngeal carcinoma via mTOR pathway.

OBJECTIVE: This study aimed to explore the mRNA and protein expression of SLC3A2 in laryngeal carcinoma cells and tissues, and functional regulatory mechanism of SLC3A2 in cell ferroptosis of laryngeal carcinoma. METHODS: We chose the key gene-SLC3A2 of DEGs from TCGA by bioinformatics analysis, and then we constructed stable knockdown of SLC3A2 in laryngeal carcinoma cells. MTT assay and clonogenic assay were used to determine cell viability and cell growth, respectively. The mRNA and protein expression were determined by RT-qPCR and western blotting, respectively. Xenograft tumor model was used to determine the role of SLC3A2 in tumor growth. RESULTS: The results of limma analysis recovered that 92 genes were involved in both upregulated DEGs and high risk of poor prognosis, whereas 36 genes were involved in both downregulated DEGs and low risk of poor prognosis. Pathway enrichment analysis indicated that mTOR signaling pathway and ferroptosis exerted a role in regulating these intersection genes. Moreover, SLC3A2 is a key gene in ferroptosis in laryngeal carcinoma. SLC3A2 is highly expressed in laryngeal carcinoma tissues and cells. Patients with high SLC3A2 expression exerted poor survival. SLC3A2 deficiency inhibited cell proliferation and foci formation. Furthermore, knockdown of SLC3A2 expression induced the efficacy of ferroptosis and suppressed ferroptosis related proteins expression. Mechanically, SLC3A2 deficiency facilitated ferroptosis through upregulating the expression of mTOR and P70S6K, whereas inhibited p-mTOR and p-P70S6K expression in laryngeal carcinoma cells. SLC3A2 deficiency inhibited tumorigenesis in nude mice. CONCLUSION: Our study suggests that SLC3A2 negatively regulates ferroptosis through mTOR pathway in laryngeal carcinoma.

Preparation of Targeted Mitochondrion Nanoscale-Release Peptides and Their Efficiency on Eukaryotic Cells.

We established a self-decomposable SiO2 encapsulated mitochondrial targeting short peptide SS31 drug loading system (SiO2@SS31) to determine its nano-sustained release characteristics in eukaryotic cells. We explored the protection of SiO2@SS31 on the 661W cells after oxidative injury by H2O2. After the drug loading, we detected the morphology of SiO2@SS31 by transmission electron microscopy (TEM). Moreover, high-pressure liquid chromatography (HPLC) was used to determine the drug capacity and encapsulation efficiency of the nanoparticles. Then, the release curve in vitro was drawn. The 661W cells were cultured in vitro to allow the detection of cytotoxicity by the MTT assay. The SS31loaded nanoscale microspheres labeled with fluorescein isothiocyanate (SiO2@FITC-SS31) were prepared, and their sustained release effect was detected with intracellular endocytosis, using confocal microscopy and flow cytometry. Within 15 days, the SiO2@SS31 nanoparticles were completely decomposed and simultaneously released the SS31 peptide in deionized water and normal saline. Nonetheless, the process was faster in simulated body fluid and serum. The MTT assay suggested that SiO2@SS31 has sustained protection compared with SS31 in the 661W cells at 48 h. Flow cytometry proved SiO2@FITC-SS31 could maintain a high level and last longer after 24 h. The SS31 peptide, which has excellent medical application prospects, can be slowly and continuously released from self-decomposable SiO2 and targeted to concentrate on mitochondria.

Synthesis, Characterization, and Specific Localization of Mitochondrial-Targeted Antioxidant Peptide SS31 Probe.

The aim of this study is to investigate the targeting efficiency of FITC-SS31 to mitochondria in both normal and H2O2-induced oxidative damaged 661W cells, characterizing the properties of FITC-SS31 in the biological assays. The purity and molecular weight of FITC-SS31 were identified using HPLC and MS. MTT and LDH assays were used to evaluate the cytotoxicity and cell permeability. The binding ability of FITC-SS31 to cells was demonstrated by flow cytometry. The colocalization of FITC-SS31 and MitoTracker both in normal and oxidative cells was analyzed by a laser confocal microscope. We detected the DEGs between SS31+H2O2 and H2O2-alone-treated cells by RNA seq. GO and KEGG analyses were performed to predict the functional gene of SS31. The molecular weight of FITC-SS31 was 1142.2 with the 97.76% purity. The flow cytometry results showed that the MFI (mean fluorescence intensity) of FITC-SS31 in normal cells in the 4 h probe treatment group was higher than that in the 2 h and the 0 h group. The MFI in the 2 h probe treatment group was much higher than that in the 4 h and 0 h groups in damaged cells. The positive rate of 10 µM FITC-SS31 was higher than that of 1 µM and 5 µM. Fluorescein imaging analysis confirmed that FITC-SS31 was overlapped with MitoTracker. Through the analysis, DEGs were highly expressed in "localization, organelle, antioxidant activity, binding" functions and enriched in "AMPK signaling pathway, MAPK targets/nuclear events mediated by MAP kinase pathway and PI3K-Akt signaling pathway." It is speculated that SS31 exerts an antioxidant effect through one of these pathways. We hypothesized that SS31 could play a more efficient role in the pathological cells in the half-life period to avoid cell death due to oxidative damage. The functions of the DEGs in SS31+H2O2 and H2O2-alone samples are related to the localization and antioxidant activity of SS31. DEGs are mostly enriched in the AMPK signaling pathway, which needs further studies.