The interaction of PRDX1 with Cofilin promotes oral squamous cell carcinoma metastasis.

Peroxiredoxin 1 (PRDX1) is an important member of the peroxiredoxin family (PRDX) and is upregulated in a variety of tumors. Previous studies have found that high PRDX1 expression is closely related to the metastasis of oral squamous cell carcinoma (OSCC), but the specific molecular mechanism is elusive. To elucidate the role of PRDX1 in the metastasis process of OSCC, we evaluated the expression of PRDX1 in OSCC clinical specimens and its impact on the prognosis of OSCC patients. Then, the effect of PRDX1 on OSCC metastasis and cytoskeletal reconstruction was explored in vitro and in nude mouse tongue cancer models, and the molecular mechanisms were also investigated. PRDX1 can directly interact with the actin-binding protein Cofilin, inhibiting the phosphorylation of its Ser3 site, accelerating the depolymerization and turnover of actin, promoting OSCC cell movement, and aggravating the invasion and metastasis of OSCC. In clinical samples and mouse tongue cancer models, PRDX1 also increased lymph node metastasis of OSCC and was negatively correlated with the phosphorylation of Cofilin; PRDX1 also reduced the overall survival rate of OSCC patients. In summary, our study identified that PRDX1 may be a potential therapeutic target to inhibit OSCC metastasis.

Impact of Detrusor Muscle Activity on Short-term Prognosis Following 1470 nm Semiconductor Laser Surgery in Elderly Patients with Benign Prostatic Hyperplasia.

Objective: To investigate the influence of preoperative detrusor muscle activity on the short-term prognosis of elderly patients diagnosed with benign prostatic hyperplasia (BPH) undergoing 1470 nm semiconductor laser surgery. Methods: A retrospective study was conducted on clinical data from 165 elderly BPH patients who underwent 1470 nm semiconductor laser surgery between May 2019 and April 2023. Patients were stratified based on preoperative urodynamic study findings, specifically their bladder contractility index (BCI). Patients with a BCI ≤100 constituted the detrusor underactivity (DU) group (n=64), while those with a BCI >100 formed the non-DU group (n=101). Surgical parameters, including duration, intraoperative blood loss, postoperative hospital stay, bladder irrigation, and catheterization duration, were compared. Additionally, changes in International Prostate Symptom Score (IPSS), Quality of Life (QOL) score, residual urine volume, and peak urinary flow rate (Qmax) were assessed before and three months after surgery in both groups. Results: There were no statistically significant differences observed between the DU and non-DU groups concerning surgical duration, intraoperative blood loss, postoperative hospitalization duration, bladder irrigation duration, and postoperative catheterization duration (P > .05). Similarly, no significant disparities were noted in the IPSS and QOL scores preoperatively and at the three-month follow-up in both groups (P > .05). Both cohorts exhibited no significant differences in residual urine volume before surgery and at the three-month mark postoperatively (P > .05). However, the postoperative Qmax was significantly reduced in the DU group compared to the non-DU group (P < .05). Conclusions: Detrusor muscle activity does not exert a significant impact on clinical symptom improvement and quality of life in elderly BPH patients treated with 1470 nm semiconductor laser surgery. However, patients with DU exhibited inferior postoperative recovery in Qmax, underscoring the importance of preoperative urodynamic studies for early intervention and enhanced surgical outcomes in this patient population.

[Analysis of a child featuring global developmental delay and autism due to variant of TBR1 gene and a literature review].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism. METHODS: A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed. RESULTS: The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c.1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+PVS1_Supporting+PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. CONCLUSION: The c.1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

IgNAR characterization and gene loci identification in whitespotted bamboo shark (Chiloscyllium plagiosum) genome.

Single domain antibodies (sdAb) are promising candidates in cancer and anti-virus biotherapies for their unique structure characters. Though VHH and IgNAR have been discovered in camelidae and nurse shark (Ginlymostoma cirratum) respectively serval decades ago, expense of these large animals still limits the studies and applications of sdAb. Recently, IgNAR has been found in whitespotted bamboo shark (Chiloscyllium plagiosum), a small-sized sharks, while how to characterize and achieved the IgNAR of whitespotted bamboo shark is still unclear. In our research, we identified four IgNAR coding gene loci in whitespotted bamboo shark chromosome 44 (NC_057753.1), and primers were designed for single domain variable regions of IgNAR (VNAR) libraries preparation. Following sequencing results revealed that all plasmids constructed with our predicted VNAR libraries contained VNAR coding sequences, which confirmed the specificities of our primers in VNAR amplification. To our surprise, ≥90% VNAR sequences were encoded by IgNAR1, which suggests IgNAR1 is the most active IgNAR transcription locus in whitespotted bamboo shark. Interestingly, we found IgNAR(ΔC2-C3) were encoded by IgNAR3. Our findings gave a new sight of whitespotted bamboo shark IgNAR, which would broad the way of IgNAR studies and applications in biotherapies.

[Genetic analysis of a child with Charlevoix-Saguenay spastic ataxia due to variant of SACS gene].

OBJECTIVE: To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). METHODS: Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases. CONCLUSION: The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.

[Nonalcoholic fatty liver disease and risk of erectile dysfunction: A bidirectional two-sample mendelian randomization study].

Objective：The purpose of this study was to explore the causal relationship between nonalcoholic fatty liver disease (NAFLD) and the risk of erectile dysfunction (ED) by using two-sample Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were screened as instrumental variables (IVs) using the public genome-wide association study summary data set (GWAS). Univariate MR, bidirectional MR and multivariate MR methods were used to analyze the causal relationship between NAFLD and ED. RESULTS: IVW results showed that NAFLD was not associated with ED (OR=0.991 2, 95%CI: 0.955 2－1.0286, P=0.640 6). The results of reverse MR showed that there was no correlation between ED and NAFLD (OR=1.181 5, 95%CI: 0.820 8－1.7007, P=0.369 5). Multivariate MR results showed that there was still no causal relationship between the two diseases after adjusting for confounding factors. CONCLUSION: The results showed that there was no causal relationship between NAFLD and the risk of ED.

[PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position improves urinary continence and protects erectile function in BPH patients].

OBJECTIVE: To evaluate the effect of transurethral plasmakinetic enucleation of the prostate (PKEP) with complete preservation of the urethral mucosa in the 11－1 o'clock position on urinary continence and erectile function in BPH patients. METHODS: We retrospectively analyzed the clinical data on 84 cases of BPH treated by traditional PKEP (group A, n = 48) or modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position (group B, n = 36) from January 2017 to December 2021. All the patients had sexual activities within three months preoperatively. We followed up the patients for 12 months after surgery and compared the baseline, surgery-related and follow-up data between the two groups of patients. RESULTS: There were no statistically significant differences between the two groups of patients in age, disease duration, prostate volume, preoperative postvoid residual urine (PVR), preoperative maximum urinary flow rate (Qmax), IPSS, PSA level, QOL scores or IIEF-5 scores, nor in the operation time, intraoperative hemoglobin decrease, volume of resected tissue, bladder flushing time, postoperative hospital stay, or postoperative improvement of Qmax and IPSS. The rate of urinary continence was significantly higher in group B than in A at 1 month postoperatively (66.67% ï¼»24/36ï¼½ vs 43.25% ï¼»20/48ï¼½, P = 0.025) and so were IIEF-5 scores at 6 months (16.69 ± 3.21 vs 15.27 ± 2.74, P = 0.032) and 12 months (18.04 ± 2.04 vs 16.96 ± 2.54, P = 0.039), while the incidence rate of retrograde ejaculation markedly lower in the former than in the latter group at 6 months (33.33% ï¼»12/36ï¼½ vs 56.25% ï¼»28/48ï¼½, P = 0.018) and 12 months (25% ï¼»9/36ï¼½ vs 47.92% ï¼»23/48ï¼½, P = 0.027). At 1, 3, 6 and 12 months after surgery, the patients in group B also showed remarkably higher QOL scores than those in group B (2.61 ± 0.81 vs 2.12 ± 0.69, P = 0.005; 2.24 ± 0.66 vs 1.94 ± 0.51,P = 0.026; 2.12 ± 0.83 vs 1.80 ± 0.53,P = 0.047; and 1.94 ± 0.65 vs 1.72 ± 0.58, P = 0.038). CONCLUSION: Modified PKEP with complete preservation of the urethral mucosa in the 11－1 o'clock position can improve urinary continence, protect erectile function and ameliorate QOL in patients with BPH.

A splicing variation in NPRL2 causing familial focal epilepsy with variable foci: additional cases and literature review.

NPRL2 (nitrogen permease regulator like 2) is a component of the GATOR1(GAP activity towards rags complex 1) proteins, which is an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. GATOR1 complex variations were reported to correlate with familial focal epilepsy with variable foci (FFEVF). However, FFEVF caused by NPRL2 variants has not been widely explored. Here, we describe a variant, 339+2T>C, in NPRL2 identified by trio whole-exome sequencing (WES) in a family. This splicing variant that occurred at the 5' end of exon 3 was confirmed by minigene assays, which affected alternative splicing and led to exon 3 skipping in NPRL2. Our cases presented multiple seizure types (febrile seizures, infantile spasms, focal seizures, or focal to generalized tonic-clonic seizures). Electroencephalogram (EEG) showed frequent discharges in the left frontal and central regions. A favorable prognosis was achieved in response to vitamin B6 and topiramate when the patient was seven months old. Our study expands the phenotype and genotype spectrum of FFEVF and provides solid diagnostic evidence for FFEVF.

[De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report].

OBJECTIVE: To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome, and to identify the possible pathogenic causes and provide evidence for clinical diagnosis. METHODS: Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital, Sichuan University. The clinical manifestations, laboratory examination and CSNK2B gene variant were analyzed. RESULTS: The main manifestations of 2 children were epilepsy, motor or intellectual retardation. Whole exon sequencing showed that CSNK2B gene c. 291+4A>T heterozygous splicing variant was found in case one, and CSNK2B copy number variation(CNV) was lost in case two. Case one received no special treatment, followed up for 8+ months, seizures and motor development were improved; case two had recurrent seizures for 9+ years, and received levetiracetam and clonazepam antiepileptic treatment. No seizures have occurred for 2 years now, and a large number of epileptic discharges can still be seen in video electroencephalogram (VEEG) with slightly backward intelligence and language development. CONCLUSION: Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder, and enrich is the CSNK2B gene variant spectrum. The pathogenesis of CSNK2B has great clinical heterogeneity, with great difference in severity of nervous system injury and different prognosis, and agenesis of corpus callosum may be one of its clinical phenotypes.

[Analysis of a case with Xia-Gibbs syndrome due to variant of AHDC1 gene].

OBJECTIVE: To analyze the clinical and genetic characteristics of a child featuring Xia-Gibbs syndrome. METHODS: Whole exome sequencing was carried out for the child. RESULTS: The patient has presented with developmental delay, hypotonia, strabismus and snoring. Cranial MRI revealed hypomyelination, while the EEGs were normal. Genetic testing revealed a de novo variant of the AHDC1 gene, namely c.730delA (p.Ile244Serfs*16), which was classified as pathogenic (PVS1+PS2+PM2). Together with 60 cases from the literature, individuals harboring a AHDC1 variant commonly have delayed motor milestones, speech delay, facial dysmorphism and hypotonia. Dysgenesis of corpus callosum is also common. In total 47 AHDC1 variants have been reported, among which truncating variants were the most common type. CONCLUSION: The c.730delA (p.Ile244Serfs*16) variant of the AHDC1 gene probably underlay the Xia-Gibbs syndrome in this patient. Above finding has provided a basis for the clinical diagnosis.

[Analysis of clinical features and ZBTB18 gene variant in a child with autosomal dominant mental disorder type 22].

OBJECTIVE: To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay. METHODS: Clinical data and laboratory examination of the patient were reviewed. Whole exome sequencing (WES) was also carried out for the family trio. RESULTS: The main manifestations of the child included global developmental delay, short stature, epileptic seizures. EEG revealed frequent occurrence of sharp (slow) waves in the right central region during sleeping, with sharp waves occasionally seen in the frontal and right posterior temporal regions. Cranial MRI has shown no obvious abnormality. WES has identified a de novo pathogenic variant in the ZBTB18 gene [NM_205768.3: exon 2: c.1282_1283del (p.Phe428Leufs*72)]. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PVS1_Moderate+PM2_Supporting). Following treatment with levetiracetam and rehabilitation, the seizures have been controlled for nearly half a year, with improvement of the psychomotor and language development. So far 28 children have been discovered with ZBTB18 gene mutations, and there was a significant difference in the clinical phenotypes of motor retardation, language retardation and epilepsy between those harboring frameshift/nonsense mutations and missense mutations. CONCLUSION: The c.1282_1283del (p.Phe428leufs *72) variant of the ZBTB18 probably underlay the autosomal dominant mental disorder type 22 in this child. Compared with missense mutations, frameshift/nonsense mutations may predispose more to motor retardation, delayed language development and epilepsy.

miR-133a-3p inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells by regulating ankyrin repeat domain 44.

In this study, we aimed to identify the specific microRNAs (miRNAs) that are involved in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) mice, and to further explore the mechanism by which these miRNAs regulate osteogenic differentiation. Based on the existing studies, the expression of seven miRNAs in BMSCs from OVX mice was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of miR-133a-3p and osteogenesis-related genes (runt-related transcription factor 2 (Runx2), Osterix, alkaline phosphatase (ALP), and osteopontin) in BMSCs treated with miR-133a-3p mimics or inhibitors was detected by qRT-PCR or Western blotting. Osteogenesis efficiency was determined using ALP and alizarin red staining. The effector-target relationship between miR-133a-3p and ankyrin repeat domain 44 (ANKRD44) was confirmed by bioinformatics and a dual luciferase assay. Among the seven selected miRNAs, miR-133a-3p expression was significantly increased in BMSCs from OVX mice. Overexpression of miR-133a-3p dramatically inhibited the expression of osteogenesis-related genes in BMSCs and reduced ALP activity and mineralization. However, these processes were markedly ameliorated upon miR-133a-3p inhibition. Moreover, miR-133a-3p appeared to target ANKRD44, and the ANKRD44 expression was negatively regulated by miR-133a- 3p. Furthermore, ANKRD44 upregulation eliminated the anti-osteogenic differentiation effects of miR-133a-3p in BMSCs. Thus, our results indicated that miR-133a-3p inhibits the osteogenic differentiation of BMSCs by suppressing ANKRD44.

[Clinical and genetic analysis of PACS2 gene variant in two child patients with developmental and epileptic encephalopathy 66].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of two children with developmental epileptic encephalopathy type 66. METHODS: Genomic DNA was extracted from peripheral blood samples of the two children and their parents. Whole exome sequencing (WES) was carried out and suspected variant was verified by Sanger sequencing. RESULTS: The main manifestations of the two children were neonatal onset seizures, hypotonia, global developmental delay, and facial dysmorphisms. Cranial MRI showed delayed myelination in case 1 and cerebellar dysgenesis in case 2. WES has identified a de novo pathogenic variant in the PACS2 gene in both patients, namely c.625G>A (p.Glu209Lys)(NM_001100913.3), which was reported as a pathogenic variant before. This variant was predicted to be pathogenic according to the American College of Medical Genetics and Genomics guideline (PS2+PM2+PP3). The seizures were controlled after combination treatment of sodium valproate and levetiracetam in both cases. At last follow-up, the motor and intellectual development of the 2 cases were improved. Compared with the cases reported, the clinical symptoms and signs of our cases were relatively mild, and the treatment effects were fairly good. CONCLUSION: The variant of c.625G>A (p.Glu209Lys) in PACS2 gene is a hotspot variant of developmental epileptic encephalopathy 66. Gene testing can facilitate the clinical diagnosis and treatment.

[Quality evaluation of Saposhnikoviae Radix based on QAMS combined with information entropy-response surface method].

This research was used with high performance liquid chromatography(HPLC), combined with information entropy-response surface method(RSM) to investigate the ethanol concentration, extraction time, liquid-to-material ratio. Taking the content of four chromogens as evaluation indexes, the weight coefficients of each index were given, and the comprehensive score was calculated to optimize the extraction process. Then, prim-O-glucosylcimifugin was used as the reference, the relative calibration factors(RCFs) of cimifugin, 4'-O-ß-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudo to prim-O-glucosylcimifugin were calculated respectively. The contents of four components in Saposhnikoviae Radix were determined by both external standard method(ESM)and quantitative analysis of multi-components by single marker(QAMS) method, and the results were compared. At last, combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to evaluate the quality of the Saposhnikoviae Radix in different production areas. The optimal extraction process parameter of the Saposhnikoviae Radix was as follows: liquid-to-material ratio is 60∶1(mL·g~(-1)), extraction time is 35 min, and ethanol concentration is 70%. The repeatability of the RCFs was perfect, and the results calculated by the QAMS were consistent with the results from the ESM. The stoichiometric results indicate that there are obvious differences in the distribution of Saposhnikoviae Radix in different production areas, and cimifugin and prim-O-glucosylcimifugin are the characteristic compounds that cause this difference. In this study, the optimal extraction process is stable and feasible, and the method of QAMS is accurate and reliable. From the perspective of four chromogens, there are differences in the quality of the Saposhnikoviae Radix in different production areas. Therefore, the established extraction process combined with the method of QAMS can be used to evaluate the quality of Saposhnikoviae Radix and provide a scientific basis for the quality control of Saposhnikoviae Radix.

Pharmacological Signatures of the Exenatide Nanoparticles Complex Against Myocardial Ischemia Reperfusion Injury.

BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury (MI/RI) is a critical cause of death in patients with heart disease. However, the pharmaco-therapeutical outcome for MI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering myocardial function in MI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of exenatide-loaded poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) nanoparticles (NPs) against MI/RI. METHODS: The size of PLL-PEG-PLL NPs and the loading and release rates of exenatide were determined. The in vitro NP cytotoxicity was evaluated using newborn rat cardiomyocytes. Rats pretreated with free exenatide or exenatide/PLL-PEG-PLL polyplexes were subjected to 0.5-h ischemia and 2-h reperfusion in the left anterior descending coronary artery. The histopathologic lesions were assessed using hematoxylin-eosin staining. The general physiological indices, including blood pressure (BP), heart rate (HR), the left ventricular ejection fraction (LVEF) and end-diastolic pressure (LEVDP), and the left ventricular pressure maximal rate of rising (dp/dtmax), were monitored using a non-invasive blood pressure analyzer and color Doppler echocardiography. The antioxidative activity in the myocardial tissue was measured. The myocardial enzymatic activity was further estimated by determining the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and glucagon-like peptide-1 (GLP-1), as well as the expression of GLP-1R in the myocardial tissue. RESULTS: Exenatide preconditioning attenuated the oxidative stress injury and promoted the myocardial function in I/R-induced myocardial injury, while the application of block copolymer PLL-PEG-PLL as a potential exenatide nanocarrier with sustained release significantly enhanced the bioavailability of exenatide. CONCLUSION: The block copolymer PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting pharmacotherapy against MI/RI with unprecedented clinical benefits. Further study is needed to better clarify the underlying mechanisms.

Discrimination of Abrus cantoniensis Hance and Abrus mollis Hance using UPLC-Q/TOF-MS and assessment of their in vivo hepatoprotective effects.

ETHNOPHARMACOLOGICAL RELEVANCE: In Guangzhou and Guangxi, China, Abrus cantoniensis Hance (AH) is known for its liver-protective properties and is commonly used in herbal teas and soups. In the herbal market and pharmaceutical preparations, AH and Abrus mollis Hance (AMH) are often used interchangeable. Despite their morphological and usage similarities, distinguishing their differences is essential for scientific research and clinical practice. AIM OF THE STUDY: This study focuses on the morphological identification, chemical composition, and hepatoprotective effectiveness of AH and AMH. It aims to evaluate their interchangeable use and provide a rationale for this practice. This research helps regulate the market of AH medicinal materials, ensuring clinical safety and effectiveness. MATERIALS AND METHODS: Samples of AH and AMH roots, stems, leaves, and seeds were collected and photographed using a stereoscope and digital imaging system. The chemical components of AH and AMH were qualitatively analyzed using UPLC-Q/TOF-MS. Chemometric techniques, such as PCA and OPLS-DA, were employed to discern the componential differences between the two species. A CCl4-induced acute liver injury mouse model was developed to assess hepatoprotective effects. The hepatoprotective properties of AH and AMH were evaluated by analyzing the liver index, H&E staining, changes in serum liver function indicators (TBIL, ALT, AST), and concentrations of SOD, MDA in liver homogenate. RESULTS: The root color, texture, stem diameter, cross-sectional characteristics, leaf shape, and seed morphology of the two plants were observed. Notable differences were identified, which can be used for accurate identification. The UPLC-Q/TOF-MS identified 50 compounds in both species, which were classified into 3 alkaloids, 22 flavonoids, 2 triterpenes, 10 triterpene saponins, 10 amides, and 3 others, and 20 different compounds between AH and AMH were screened by chemometrics. By improving serum biomarkers (ALT, AST, TBIL) and regulating oxidative stress markers (SOD, MDA), the alleviating effect of AH and AMH extracts on liver injury was confirmed. Notably, AH showed a stronger liver protective effect, significantly reducing ALT and AST levels more than AMH. CONCLUSION: This study enhances understanding of the morphological identification, chemical profiling, and hepatoprotective effects of AH and AMH. It provides a reference for future scientific research and the clinical application of AH in treating liver damage.

Optimization of Extraction and Quality Evaluation of Abri Herba by Response Surface Methodology Combined with Quantitative Analysis of Multi-Components by a Single Marker.

BACKGROUND: Abri Herba (AH) is a famous medicinal and edible traditional Chinese medicine, which is usually used for liver disease. To date, few studies have been conducted on the ultrasonic extraction (UAE) process for AH and the application of quality analysis of multi-components by the single-marker (QAMS) method to evaluate the quality. OBJECTIVE: To optimize the UAE process for AH, and develop and validate the quality evaluation of AH by the QAMS method. METHODS: The UAE conditions of AH were optimized by response surface methodology with the total contents of protocatechuic acid, hydantoin, gardeniaine, vicenin-2, salvoside and isosalvoside as indicators, the ultrasonic time, methanol concentration and liquid to material ratio as parameters. The content of protocatechuic acid, hypaphorine, abrine, vicenin-2, schaftoside, and isoschaftoside in 12 batches of AH was first determined by the external standard method (ESM) using HPLC. After that, based on abrine as the internal standard, the relative correction factors (RCF) for protocatechuic acid, hypaphorine, vicenin-2, schaftoside and isoschaftoside were established, and the ESM method was used to verify the QAMS method. RESULTS: The results show that the optimal extraction process parameters for AH are an ultrasonic time of 22 min, a methanol concentration of 45%, and liquid to material ratio of 26 (mL/g). The QAMS results show that the relative correction factor has good reproducibility, and there is no significant difference between the results of the ESM method and the QAMS method for each chemical constituent, indicating that the research is feasible. CONCLUSION: The optimized extraction process of AH and the established QAMS-based quality control method are stable and can be used for the quality control of AH. HIGHLIGHTS: A response surface methodology was used to optimize the ultrasonic extraction process for AH, and a QAMS method was established for evaluating the quality of AH.

Azoxystrobin induces apoptosis via PI3K/AKT and MAPK signal pathways in oral leukoplakia progression.

Background: Oral leukoplakia (OLK) is one of the oral potentially malignant disorders (OPMDs) with an increased risk of developing oral squamous cell carcinoma (OSCC). There is no ideal therapeutic drug yet. Our previous study showed azoxystrobin (AZOX) inhibited the viability of OLK cells and the incidence of mouse tongue cancer. However, its specific mechanism has not been clarified. Here, we used network pharmacology with experimental validation to investigate the roles and mechanisms of AZOX in OLK. Methods: The targets of AZOX and OLK were obtained from online databases. The overlapping genes were identified by the Jvenn database. STRING and Cytoscape software were used to construct the PPI network. GO and KEGG enrichment analyses were used to analyze the biological function. Molecular docking and CETSA were used to verify the direct binding between AZOX and its key targets. 4NQO induced mouse tongue carcinogenesis model was constructed to clarify the treatment response of AZOX in vivo. TUNEL staining was performed to detect the effect of AZOX on apoptosis in mouse OLK tissues. CCK8 assay, flow cytometry, and western blot were used to detect the effect of AZOX on cell proliferation and apoptosis in DOK cells. The expression of PI3K/AKT and MAPK markers were analyzed by immunohistochemistry in vivo or by western blot in vitro. Results: Venn diagram showed 457 overlapping targets, which were involved in the PI3K/AKT, MAPK, and apoptosis pathways, and the top 5 hub modules were TP53, STAT3, AKT1, MAPK1, and PIK3R1. AZOX was bound with the highest force to AKT and PI3K by AutoDock Vina. PyMOL software visualized that AZOX could fit in the binding pocket of the AKT and PI3K. The carcinogenesis rate of the mouse OLK in the high-dose AZOX group was significantly reduced. AZOX induced apoptosis in the OLK tissues and DOK cells, and the expression of PI3K, AKT, p-ERK was decreased, and the expression of p-p38 and p-JNK was increased. CETSA indicated that AZOX might have a direct binding with AKT and PI3K. Conclusion: AZOX may induce apoptosis via PI3K/AKT and MAPK pathways in OLK. This study reveals the potential therapeutic targets of AZOX in OLK.

Prenatal exposure to antibiotics and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis.

Background and purpose: A growing body of research suggests that inflammation and maternal infections may lead to an increased risk of neurodevelopmental problems such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), cerebral palsy (CP), and epilepsy in offspring. The aim of this study was to observe the connection between prenatal antibiotic exposure and the risk of these neurodevelopmental disorders in offspring. Patients and methods: A comprehensive search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Google Scholar, and Scopus databases for observational studies that looked into the link between prenatal exposure to antibiotics and the risk of neurodevelopmental problems in offspring, published from 1 January 1950 to 31 January 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Data were analyzed using the STATA version 12 software, and an odds ratio (OR) with a 95% confidence interval (CI) was reported. Results: A total of 15 studies were included in the meta-analysis. Prenatal antibiotic exposure was associated with the increased risk of ADHD (OR = 1.14; 95% CI = 1.13 to 1.15; I 2 = 0%) and epilepsy (OR = 1.34; 95% CI = 1.02 to 1.66; I 2 = 96.8%). The link between prenatal antibiotic exposure and the risk of ASD [OR = 1.09; 95 % CI = 0.88 to 1.31; I 2 = 78.9%] and CP [OR = 0.99; 95% CI = 0.56 to 1.43; I 2 = 91%] was found to be non-significant. In all of the included prospective cohort studies, subgroup analysis suggested a significant association between prenatal antibiotic exposure and the incidence of ASD [OR = 1.17; 95% CI = 1.03 to 1.31; I 2 = 48.1%] and CP [OR = 1.18; 95% CI = 1.02 to 1.34; I 2 = 0%]. Conclusion: Prenatal antibiotic exposure during pregnancy is linked to a higher incidence of ADHD and epilepsy in the offspring. Further prospective studies that compare prenatal antibiotic use and are adjusted for various confounders are needed to further assess the association of prenatal antibiotic exposure and neurological disorders in offspring. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022306248.

Rare variant of TBL1XR1 in West syndrome: A case report.

BACKGROUND: West syndrome (WS) is an epileptic encephalopathy (EE) that begins in children 4-7 months of age (in rare cases older than 2 years). To date, over 30 genes that have been reported to be related to WS. Reports involving the extremely rare pathogenic gene, transducin beta-like 1-X- linked receptor 1(TBL1XR1) are quite limited. METHODS: We performed exome sequencing (ES) of family trios for this infant. We also collected and summarized the clinical data for reported heterozygous germline variants of TBL1XR1. Moreover, we reviewed all published cases and summarized the clinical features and genetic variants of TBL1XR1. RESULTS: ES revealed a de novo variant in TBL1XR1 [NM_024665.5: exon4: c.187G > A (p.Glu63Lys)]. This variant was classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and was verified by Sanger sequencing. Further conservation analyses revealed a high conservation among several species. There was clinical heterogeneity among all patients with TBL1XR1-related West syndrome. CONCLUSION: Our results expand the pathogenic variant spectrum of TBL1XR1 and strengthen the pathogenic evidence of TBL1XR1 in West syndrome.