Long non-coding RNA MAGEA4-AS1 binding to p53 enhances MK2 signaling pathway and promotes the proliferation and metastasis of oral squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) regulate the occurrence, development and progression of oral squamous cell carcinoma (OSCC). We elucidated the expression features of MAGEA4-AS1 in patients with OSCC and its activity as an OSCC biomarker. Furthermore, the impact of up-regulation of MAGEA4-AS1 on the cellular behaviors (proliferation, migration and invasion) of OSCC cells and intrinsic signal mechanisms were evaluated. Firstly, we analyzed MAGEA4-AS1 expression data in The Cancer Genome Atlas (TCGA) OSCC using a bioinformatics approach and in 45 pairs of OSCC tissues using qPCR. Then CCK-8, ethynyl deoxyuridine, colony formation, transwell and wound healing assays were conducted to assess changes in the cell proliferation, migration and invasion protential of shMAGEA4-AS1 HSC3 and CAL27 cells. The RNA sequence of MAGEA4-AS1 was identified using the rapid amplification of cDNA ends (RACE) assay. And whole-transcriptome sequencing was used to identify MAGEA4-AS1 affected genes. Additionally, dual-luciferase reporter system, RNA-binding protein immunoprecipitation (RIP), and rescue experiments were performed to clarify the role of the MAGEA4-AS1-p53-MK2 signaling pathway. As results, we found MAGEA4-AS1 was up-regulated in OSCC tissues. We identified a 418 nucleotides length of the MAGEA4-AS1 transcript and it primarily located in the cell nucleus. MAGEA4-AS1 stable knockdown weakened the proliferation, migration and invasion abilities of OSCC cells. Mechanistically, p53 protein was capable to activate MK2 gene transcription. RIP assay revealed an interaction between p53 and MAGEA4-AS1. MK2 up-regulation in MAGEA4-AS1 down-regulated OSCC cells restored MK2 and epithelial-to-mesenchymal transition related proteins' expression levels. In conclusion, MAGEA4-AS1-p53 complexes bind to MK2 promoter, enhancing the transcription of MK2 and activating the downstream signaling pathways, consequently promoting the proliferation and metastasis of OSCC cells. MAGEA4-AS1 may serve as a diagnostic marker and therapeutic target for OSCC patients.

Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND AND AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare, with limited evidence regarding endoscopic treatment. This study investigated the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluated long-term outcomes, including local recurrence and metastasis. METHODS: Seventy-eight patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. Clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En-bloc resection was achieved for 74 tumors (94.9%) and R0 resection for 68 tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥10 mm, and muscularis propria invasion as risk factors for noncurative resection. Two patients with R1 resection (vertical margin involvement) and 2 patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including 2 cases of delayed bleeding and 2 cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in 1 patient with R1 resection 3 months after the original procedure. CONCLUSIONS: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

Health risk assessment of triazole fungicides around a pesticide factory in China.

The environmental pollution and health effects caused by pesticide production have consistently garnered considerable research interest. In the present study, the concentrations of five triazole fungicides (TFs) in air, indoor dust, and diet were monitored around a pesticide factory in eastern China from November 2020 to May 2021. The levels of five TFs in each sample were determined via UPLC‒MS/MS. For a health risk assessment, the United States Environmental Protection Agency's deterministic method was applied. The findings revealed that the total concentrations of the five TFs around the monitoring area ranged from 0.29 to 5.85 ng/m3 in outdoor air, 287.4 to 9878.5 µg/kg in indoor dust, 0.0578 to 4.948 µg/kg in vegetables, and 0.447 to 3.00 µg/kg in rice. Notably, tebuconazole and hexaconazole had consistently high contributions over the years. For adults and children, the average daily doses (ADDs) were 1.32 × 10-5 and 2.69 × 10-5 mg/kg/day, respectively, in the monitoring area and 4.25 × 10-6 and 6.42 × 10-6 mg/kg/day, respectively, in the control area. In the control area, rice and vegetables were the primary media for exposure to TFs in children and adults, collectively accounting for more than 94% of the total TF exposure. Conversely, indoor dust is identified as the main medium of TF exposure in children residing near the pesticide factory, representing approximately 40% of the total exposure. The risks of noncarcinogenic effects on children and adults in the monitoring area were significantly greater than those in the control area, being approximately ten times greater for children, warranting increased attention. The carcinogenic risk to human health is relatively safe.

Seven Immune-Related Genes' Prognostic Value and Correlation with Treatment Outcome in Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is a growing concern worldwide, due to its poor prognosis, low responsiveness to treatment, and drug resistance. Since immunotherapy effectively improves HNSCC patients' survival status, it is important to continuously explore new immune-related predictive factors to accurately predict the immune landscape and clinical outcomes of individuals suffering from HNSCC. Methods: The HNSCC transcriptome profiling of RNA-sequencing data was retrieved from TCGA database, and the microarray of GSE27020 was obtained from the GEO database for validation. The differentially expressed genes (DEGs) between HNSCC and normal samples were identified by multiple test corrections in TCGA database. The univariate and multivariate Cox analyses were performed to identify proper immune-related genes (IRGs) to construct a risk model. The Cox regression coefficient was employed for calculation of the risk score (RS) of IRG signature. The median value of RS was utilized as a basis to classify individuals with HNSCC into high- and low-risk groups. The Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed for the identification of the prognostic significance and precision of the IRG signature. The signature was also evaluated based on clinical variables, predictive nomogram, mutation analysis, infiltrating immune cells, immune-related pathways, and chemotherapeutic efficacy. The protein-protein interaction (PPI) network and functional enrichment pathway investigations were utilized to explore possible potential molecular mechanisms. Finally, the hub gene's differential mRNA expression levels were evaluated by means of the Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA) was utilized for the validation of their translational levels. Results: Collectively, 1593 DEGs between HNSCC and normal samples were identified, of which 136 IRGs were differentially expressed. Then, the 136 immune-related DEGs were mostly enriched in the cytokine-related signaling pathways by GO and KEGG analyses. After that, a valuable signature based on seven genes (DKK1, GAST, IGHM, IL12RB2, SLURP1, STC2, and TNFRSF4) was designed. The HNSCC patients into the low-risk group and the high-risk group were divided by using the median RS; the HNSCC patients in the high-risk group had a worse survival than those in the low-risk group. The risk signature was verified to be an independent predictive marker for HNSCC patients. Meanwhile, the RS had the largest contribution to survival of these patients based on the predictive nomogram. In addition, the low-risk HNSCC patients exhibited significantly enriched immune cells, along with an association with high chemosensitivity. Conclusion: The constructed gene signature can independently function as a predictive indicator for the clinical features of HNSCC patients. The low-risk HNSCC subjects might benefit from immunotherapy and chemotherapy.

Interactions among maternal smoking, breastfeeding, and offspring genetic factors on the risk of adult-onset hypertension.

BACKGROUND: Previous studies have reported that maternal smoking during pregnancy and breastfeeding may affect the occurrence of hypertension, but whether early life factors modify the impact of the offspring's genetic risk on hypertension is still unknown. The aim of this study was to investigate the relationships among maternal smoking and breastfeeding with adult-onset hypertension and the modified impact of offspring genetic susceptibility. METHODS: This study included 437,185 participants from the UK Biobank who were initially free of hypertension and provided a prospective cohort of individuals aged 40 to 69 years. The association of maternal smoking during pregnancy and breastfeeding with hypertension was examined by using the Cox regression model. Then, a polygenic risk score (PRS) for hypertension was used to test the gene-environmental interaction on hypertension. RESULTS: During a median follow-up period of 8.7 years, a total of 68,148 cases of hypertension were identified in this study. The hazard ratios (HRs) and 95% confidence intervals (CIs) of hypertension for maternal smoking and breastfeeding were 1.11 (1.09, 1.13) and 0.96 (0.94, 0.98), respectively. However, no evidence of an interaction between maternal smoking and breastfeeding was observed. Across all levels of genetic risk, including high genetic risk, maternal smoking and nonbreastfeeding had higher hypertension hazards than nonmaternal smoking and breastfeeding, respectively. The adjusted HRs (95% CIs) of hypertension were 1.80 (1.73, 1.87) in those who had high genetic predisposition plus maternal smoking and 1.67 (1.60-1.74) in those with nonbreastfeeding and high genetic risk. There were significant additive interactions between maternal smoking or breastfeeding and genetic factors on the incidence of hypertension. CONCLUSIONS: Maternal smoking and nonbreastfeeding were associated with a higher risk of hypertension in adulthood and may attenuate the risk of hypertension related to genetic factors. These results suggested that adherence to nonmaternal smoking and breastfeeding was associated with a lower risk of hypertension among participants with all gradients of genetic risk.

Melatonin attenuates polystyrene microplastics induced motor neurodevelopmental defect in zebrafish (Danio rerio) by activating nrf2 - isl2a Axis.

Microplastics, a new type of ecological pollutant, have now become a major environmental concern worldwide. Polystyrene microplastics (PS), one of the most abundant form of microplastics, cause deleterious effects across species. Melatonin (MT), which is secreted by pineal gland, exhibits protective role against pollutant-induced damage. However, whether MT could ameliorate PS-induced neurodevelopmental toxicity remain unclear. In our study, zebrafish embryos were treated with PS (0.5, 25 mg/L) in the presence or absence of MT (1 µM) from 4 h post-fertilization (hpf) to 144 hpf. Locomotion behavior, oxidative stress, apoptosis, proliferation and development of caudal primary (Cap) motoneuron axon were analyzed. Gene expression was determined by qRT-PCR or whole-mount in situ hybridization. Results showed that PS exposure significantly reduced swimming speed of zebrafish larvae and induced excessive reactive oxygen species (ROS), apoptosis and aberrant proliferation. In addition, PS treatment markedly shortened the length of Cap motoneuron axons and decreased expression of neurodevelopment related genes. While, MT administration considerably rescued the neurodevelopmental toxicity of PS. Mechanistically, MT activated nrf2 (nuclear factor-E2-related factor 2) - isl2a (ISL LIM homeobox 2a) axis to antagonize the side effects of PS. In all, our findings suggest that PS exposure during early life lead to aberrant neurodevelopment of zebrafish, and MT might be a therapeutic option for protecting such disorder.

Silencing circular RNA hsa_circ_009755 promotes growth and metastasis of oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is a common and rampant malignancy of the head and neck. However, its pathogenesis remains unclear. In this study, we have investigated the effects of circular RNA hsa_circ_009755 on proliferation, migration, invasion, and apoptosis in OSCC cells in vitro. METHOD: Eight pairs of OSCC and normal adjacent tissues were selected to detect the differential expression of circRNAs by high-throughput sequencing. circRNA hsa_circ_009755 expression was determined by quantitative real-time polymerase chain reaction in OSCC tissues and cell lines. CCK-8, wound healing, Transwell, and flow cytometry assays were used to determine OSCC cell proliferation, migration, invasion, and apoptosis, respectively. RESULT: The expression of hsa_circ_009755 was low in OSCC tissues and three OSCC cell lines. Silencing hsa_circ_009755 significantly enhanced the proliferation, migration, and invasion and suppressed the apoptosis of OSCC cells. CONCLUSION: Therefore, hsa_circ_009755 may be important in the tumorigenesis of OSCC.

The catalytic subunit of DNA polymerase δ is a nucleocytoplasmic shuttling protein.

The DNA polymerase δ catalytic subunit (PolD1) is a highly conserved protein with established functions in both the nucleus and the cytoplasm: whereas PolD1 participates in the replication and repair of nuclear DNA, it plays a role in the control of cytoplasmic microtubule growth by directly acting on microtubule-nucleator γ-tubulin ring complexes. Here, we show that PolD1 shuttles between the nucleus and the cytoplasm. PolD1 harbors two nuclear localization signals that mediate the active transport of PolD1 to the nucleus; conversely, PolD1 is exported from the nucleus by the exportin CRM1-dependent mechanism, a major nuclear-export pathway that mediates the export of various cargos. These findings suggest that the nucleocytoplasmic distribution of PolD1 is influenced by both the nuclear import and export activities of the protein.

Long non-coding RNA highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy that exhibits high incidence worldwide. In diverse human cancers, the long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) is aberrantly expressed, but how HULC affects OSCC development and progression has remained mostly unknown. We report that HULC was abnormally up-regulated in oral cancer tissues and OSCC cell lines, and that suppression of HULC expression in OSCC cells not only inhibited the proliferation, drug tolerance, migration and invasion of the cancer cells, but also increased their apoptosis rate. Notably, in a mouse xenograft model, HULC depletion reduced tumorigenicity and inhibited the epithelial-to-mesenchymal transition process. Collectively, our findings reveal a crucial role of the lncRNA HULC in regulating oral cancer carcinogenesis and tumour progression, and thus suggest that HULC could serve as a novel therapeutic target for OSCC.

Circular RNA hsa_circ_0007059 indicates prognosis and influences malignant behavior via AKT/mTOR in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), the most common oral cancer, damages oral epithelial cells after the accumulation of multiple genetic mutations. Although emerging evidence supports the key role of circular RNAs (circRNAs) in various malignancies, the clinical value and function of circRNAs in OSCC remain unclear. In this study, patients with OSCC (n = 8) and controls ( n = 8) were compared using high-throughput sequencing and microarray circRNA expression profiles. The circRNA hsa_circ_0007059 was downregulated in OSCC. Subsequently, hsa_circ_0007059 levels in OSCC tissues and cell lines were assessed by quantitative reverse-transcription chain reaction. Loss-of-function and gain-of-function experiments were performed to determine whether hsa_circ_0007059 affects malignant behavior in SCC15 and CAL27 cells. Importantly, hsa_circ_0007059 upregulation suppressed cell growth, migration, and invasion, facilitating apoptosis of these cells. Furthermore, nude mouse tumor formation was assessed to validate the tumor-suppressive role of hsa_circ_0007059 in vivo. Finally, hsa_circ_0007059 was determined to alter cell growth via AKT/mTOR signaling, representing a potential prognostic/therapeutic target for OSCC.

Circular RNA hsa_circ_0055538 regulates the malignant biological behavior of oral squamous cell carcinoma through the p53/Bcl-2/caspase signaling pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common oral and maxillofacial malignant tumor with high rates of metastasis and mortality. Circular RNAs (circRNAs), a type of non-coding RNA, are involved in the development of a variety of tumors. The roles of circRNAs in OSCC are unclear; in this study, the correlation between the circRNA hsa_circ_0055538, previously identified by high-throughput sequencing, and the biological behavior of OSCC was evaluated. METHODS: circRNA expression was evaluated using patient tissue samples and various OSCC cell lines. The effects of overexpression and knockdown were evaluated by lentiviral infection and siRNA transfection of the SCC9 and CAL27 cell lines. Migration, invasion, apoptosis, and the expression of proteins in the p53 signaling pathway were evaluated. Infected cells were injected into nude mice to evaluate tumorigenesis. RESULTS: Low hsa_circ_0055538 expression levels were verified in tumor tissues and OSCC cell lines. Clinical data analysis showed that the expression level is related to the degree of tumor differentiation. Lentiviral infection and siRNA transfection of SCC9 and CAL27 cell lines revealed that changes in circRNA expression significantly affected the malignant biological behavior of OSCC cells. Importantly, nude mouse experiments showed that high expression of hsa_circ_0055538 inhibited tumor growth. Finally, hsa_circ_0055538 may affect the development of OSCC via the p53/Bcl-2/caspase signaling pathway. CONCLUSIONS: Our results indicated that hsa_circ_0055538 is involved in OSCC via the p53 signaling pathway and may be a diagnostic and/or prognostic marker as well as a therapeutic target.

Hsa_circ_0005379 regulates malignant behavior of oral squamous cell carcinoma through the EGFR pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown. METHODS: By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of circRNA hsa_circ_0005379 on OSCC tissues and cell lines was monitored by qRT-PCR, Transwell assay, flow cytometry, and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival. RESULTS: We found that circRNA hsa_circ_0005379 expression is significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of hsa_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro and suppresses OSCC growth in nude mice in vivo. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of the epidermal growth factor receptor (EGFR) pathway. Furthermore, we found that high expression of hsa_circ_0005379 could significantly enhance the sensitivity of OSCC to the cetuximab drug. CONCLUSIONS: Our findings provide evidence that hsa_circ_0005379 regulates OSCC malignancy and may be a new therapeutic target for OSCC treatment.

[Penile necrosis resulting from post-circumcision microwave diathermy: A report of 9 cases].

OBJECTIVE: To investigate the pathogenesis and treatment of penile necrosis resulting from microwave diathermy following circumcision. METHODS: We retrospectively analyzed the clinical data about 9 cases of penile necrosis resulting from postoperative microwave diathermy following circumcision. The 9 males, aged 20 - 39 (mean 26) years, underwent traditional circumcision for redundant prepuce or phimosis in other hospitals, followed by microwave diathermy for 30 - 60 minutes daily, which resulted in penile necrosis. With no response to conservative therapy, the patients were referred to our hospital at 3 -30 days postoperatively. Of the 9 patients, 5 presented with dry gangrene and 4 with moist gangrene. Six of the patients underwent partial penectomy, including 1 that received penis lengthening.3 months later, while the other 3 underwent total penectomy for total penile necrosis followed by penile reconstruction 3 months later, with deep inferior epigastric perforator (DIEP) flaps and by implantation of the 12th costal cartilage in 2 cases and with epigastric groin island flaps and by urethroplasty in the other. RESULTS: The patients were followed up for 2 - 8 years, and all could urinate smoothly in the standing position. Of the 6 men treated by partial penectomy, 1 received penis lengthening and achieved a penile length of 7 cm and 5 had the remaining penile length of 3 -5 cm, 4 with erectile function and the other 2 capable of sexual intercourse. The 3 men treated by total penectomy achieved nearly normal external appearance of the penis, with a finalized length of (11.7 ± 1.3) cm, a circumference of (11.4 ± 2.1) cm, and a normal feel of the skin. Of the 3 cases of penile reconstruction, 2 achieved sufficient erectile hardness of the penis (grade 3) for sexual intercourse, while the other 1 remained impotent. CONCLUSION: Post-circumcision microwave diathermy may result in penile necrosis, for the management of which, early debridement is necessitated and penile lengthening or reconstruction can be performed according to the severity of the lesion and needs of the patient.

Serum metabolism distribution in individuals exposed to dioxins: A case study of residents near the municipal solid waste incinerators in China.

Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) have attracted considerable attention owing to their environmental persistence, bioaccumulation, and high toxicity. This study aimed to investigate changes in serum metabolites following exposure to PCDD/Fs and to reveal a novel pathogenesis of PCDD/Fs. Serum samples were collected from 75 residents living near a municipal solid waste incinerator in China to analyse the relationship between PCDD/Fs and serum metabolic components. The serum level in the low-exposure group [19.07 (13.44-23.89) pg-TEQ/L] was significantly lower than that in the high-exposure group [115.60 (52.28-592.65) pg-TEQ/L]. Non-targeted metabolomic studies based on liquid chromatography-high resolution mass spectrometry have been applied to the metabolomic analysis of serum. Thirty-seven metabolites with significant differences among the different groups were identified as biomarkers. Pathway analysis revealed that high dioxin exposure perturbed various biological processes, including glycerol phospholipid metabolism and the interconversion of pentose and glucuronate. The results of a population health survey showed that the serum dioxin concentration in patients with diabetes was significantly higher than that in the control population. These findings suggest that dioxin exposure is associated with several potential adverse health risks, including inflammation, diabetes, and cardiovascular disease, through metabolic changes.

Oxidative damage and cardiotoxicity induced by 2-aminobenzothiazole in zebrafish (Danio rerio).

There is limited information available on cardiovascular toxicity of 2-Aminobenzothiazole (NTH), a derivative of benzothiazole (BTH) commonly used in tire production, in aquatic organisms. In the present study, the zebrafish embryos were exposed to varying concentrations of NTH (0, 0.05, 0.5, and 5 mg/L) until adulthood and the potential cardiovascular toxicity was assessed. NTH exposure resulted in striking aberrations in cardiac development, including heart looping failure and interference with atrioventricular canal differentiation. RNA-sequencing analysis indicated that NTH causes oxidative damage to the heart via ferroptosis, leading to oxygen supply disruption, cardiac malformation, and ultimately, zebrafish death. Quantitative real-time polymerase chain reaction (qPCR) analysis demonstrated the dysregulation of genes associated with early heart development, contraction, and oxidative stress. Additionally, reactive oxygen species accumulation and glutathione/malondialdehyde levels changes suggested a potential link between cardiac developmental toxicity and oxidative stress. In adult zebrafish, NTH exposure led to ventricular enlargement, decreased heart rate, reduced blood flow, and prolonged RR, QRS, and QTc intervals. To the best of our knowledge, this study is the first to provide evidence of cardiac toxicity and the adverse effects of ontogenetic NTH exposure in zebrafish, revealing the underlying toxic mechanisms connected with oxidative stress damage. These findings may provide crucial insights into the environmental risks associated with NTH and other BTHs.

Severe hematuria after transurethral electrocoagulation in a patient with an arteriovesical fistula.

BACKGROUND: Arteriovesical fistulas are extremely rare. Only eleven cases were previously reported in the literature. They can occur iatrogenically, traumatically or spontaneously. CASE PRESENTATION: We report an unusual case of a 62-year-old woman with arteriovesical fistula that developed fatal hematuria after transurethral electrocoagulation. Computed tomography (CT) and selective angiography revealed a pseudoaneurysm of the right superior vesical artery with arteriovesical fistula formation, which was managed by transarterial embolization. CONCLUSIONS: Contrast enhanced CT or CT angiography should be performed when a pulsatile hemorrhage is revealed during cystoscopy. Therapeutic vesical arterial embolization should be considered as a safe and effective procedure for arteriovesical fistulas. Transurethral electrocoagulation may cause severe hematuria for pulsatile bladder bleeding in patients with pelvic vascular malformation.

Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis.

Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy. Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan. Methods: We conducted a systematic search (unlimited initial date to 22 October 2022) in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment. Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy (RR = 1.28, 95%CI:1.17 to 1.39), reduce blood pressure [systolic blood pressure (MD = 8.98, 95%CI:-12.38 to -5.59); diastolic blood pressure (MD = 5.74, 95%CI:-7.20 to -4.29)], serum creatinine (MD = -17.32, 95%CI:-20.55 to -14.10), blood urea nitrogen (MD = -1.89, 95%CI:-3.76 to -0.01), urine microalbumin (MD = -23.90, 95%CI:-26.54 to -21.26), and urinary protein to creatinine ratio (MD = -1.92, 95%CI:-2.15 to -1.69), cystatin C (MD = -1.04, 95%CI: -1.63 to -0.45) and increase calcitonin gene-related peptide (MD = 18.68, 95%CI:12.89 to 24.46) without increasing adverse reactions (RR = 2.20, 95%CI:0.52 to 9.40). But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low. Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256.

Inhibition of human oral squamous cell carcinoma proliferation and migration by prodrug-activating suicide gene therapies.

Head and neck squamous cell carcinoma (HNSCC), which originates from mucosal epithelium in the oral cavity, pharynx and larynx, is the sixth most common malignancy in the world. The prognosis of HNSCC is not satisfactory due to metastasis, resulting in 5-year survival rates ranging from 65.9 to 67.2%. Previously, we developed a method to evaluate the effect prodrug-activating suicide gene (PA-SG) therapy on the proliferation of HNSCC. The present study investigated PA-SG therapy on metastatic HNSCC by wound-healing assay and our previously established method. HSC-3 cells with stable expression of suicide genes thymidine kinase (TK) or cytosine deaminase (CD) were treated with prodrugs ganciclovir (GCV) or 5-fluorocytosine (5-FC), respectively. Both GCV and 5-FC inhibited HSC-3 proliferation while the bystander effect of CD/5-FC was greater compared with that of TK/GCV. GCV showed a greater anti-migration effect compared with that of 5-FC. To the best of our knowledge, the present study is the first to evaluate the anti-migratory and anti-proliferative effects of PA-SG therapies on metastatic HNSCC. This may also serve as a general method to quantify other types of PA-SC therapy. The present results demonstrated that PA-SG therapy is a promising treatment for anti-metastatic HNSCC therapy development.