Constituents from Chloranthus multistachys and their cytotoxic activities against various human cancer cell lines.

Two new furanoeremophilane sesquiterpenoids, namely, 6,9-dioxo-1α,4α-dihydroxy-furanoeremophilane (1) and 4α,5α-epoxy-6,9-dioxo-1α-hydroxyl-furanoeremophilane (2), and 10 known compounds were isolated from the whole plant of Chloranthus multistachys, and compound 3 was converted to derivative 3a. Their structures were determined based on extensive spectroscopic analysis. All compounds were evaluated by using five cancer cell lines: PC3, LNcap, A549, K562, and HEL. The derivative 3a exhibited excellent cytotoxic activities, with the IC50 against HEL cells being the lowest at 1.322 ± 0.08 µM, which was comparable to that of the positive control (doxorubicin). Mechanism studies showed that the anticancer activity of 3a may be associated with cell cycle regulation.

Two new polyoxy steroidal glycosides from the roots of Dregea sinensis Hemsl.

Two new polyoxy steroidal glycosides, named as 11- O-α-acetyl-12-O-ß-tigloyl- 3ß,14ß-dihydroxy-pregn-5-en-20-one-3-O-ß-D-oleadropyranosyl-(1→4)-ß-D-6-deoxy-3-O-methyl-allopyanoside (1) and 11- O-α-acetyl -12-O-ß-benzoate-3ß, 14ß-dihydroxy-pregn-5-en- 20-one-3-O-ß-D-oleadropyranosyl-(1→4)-ß-D-6-deoxy-3-O-methyl-allopyanoside (2) were isolated from the roots of Dregea sinensis Hemsl. Their structures were elucidated by various spectroscopic techniques including UV, IR, HRESIMS, 1 D and 2 D NMR. All the two compounds were tested for their cytotoxic activity in vitro, and the result showed that compounds 1-2 displayed moderated cytotoxic activity against HL-60 cell line with IC50 values of 18.4 µM and 23.9 µM, respectively. [Formula: see text].

The influence of diet quality and dietary behavior on health-related quality of life in the general population of children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: The association between diet quality, dietary behavior and health-related quality of life has been mostly examined in children and adolescents with specific chronic diseases. No systematic review has synthesized the influence of diet quality and dietary behavior on health-related quality of life in the general population of children and adolescents. The purpose of this study was to systematically review the primary studies that evaluated the association between diet quality, dietary behavior and health-related quality of life in the general population of children and adolescents and to synthesize the findings for the association. METHODS: A computer search in the databases of MEDLINE, EMBASE and PSYCINFO was performed to retrieve English language studies that were published from 1946 up to April 8, 2018. We also screened the PubMed-related articles and the reference lists of the existing relevant literature to identify other eligible studies. We synthesized the association between diet quality, dietary behavior and health-related quality of life using both a qualitative method and meta-analysis. We reported the review following up the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. RESULTS: Seventeen studies were included in the synthesis including twelve cross-sectional studies and five longitudinal studies. We found that diet quality and dietary behavior were associated with health-related quality of life in children and adolescents. The positive effect of healthy diets on health-related quality of life was observed for multiple domains of health-related quality of life, including physical, school and emotional functioning, and psychosocial quality of life. We observed a dose-response relationship between the diet exposure and health-related quality of life, where an unhealthy dietary behavior or lower diet quality was associated with decreased health-related quality of life among children and adolescents. CONCLUSION: The findings of the systematic review suggest the importance of promoting healthy diets and nutrition for good health-related quality of life among children and adolescents. Future research is needed to strengthen the evidence for prospective relationships and for the dose-response effect between diet quality, dietary behavior and health-related quality of life among children and adolescents.

Clinical features and surgical results of cardiac myxoma in Carney complex.

BACKGROUND: We sought to analyze clinical features and surgical results of 10 cases of cardiac myxomas in Carney complex (CNC). METHODS: Between January 2003 and December 2013, 10 patients with cardiac myxomas in CNC underwent surgical resection. Associated cardiac lesions included moderate and severe mitral regurgitation in two cases, and moderate tricuspid regurgitation in one case. Age, gender, the incidence of arterial embolism, the rate of multiple cardiac myxomas, and the recurrence rate after resections of cardiac myxoma were compared between isolated cardiac myxomas and cardiac myxomas in CNC. RESULTS: The incidence of cardiac myxoma in CNC was 1.74% (10/574). There were no deaths following surgery. There was one late death due to cerebral embolism 40 months following a reoperation (10%). A significant difference was found in the age, the incidence of arterial embolism, the rate of multiple cardiac myxomas, and the recurrence rate after resection of cardiac myxoma between cardiac myxoma in CNC and isolated cardiac myxoma (P < 0.05). There was no significant difference in gender between cardiac myxoma in CNC and isolated cardiac myxoma (P > 0.05). CONCLUSIONS: Complex myxomas in CNS present at an earlier age, are more prevalent in women than in men, are more often multicentric, with a higher rate of arterial embolism and a high recurrence rate after resection. Close follow-up for cardiac myxoma in CNC after surgery is necessary due to the high recurrence rate.

Surgical treatment for Kommerell's diverticulum associated with aortic dissection involving aortic arch.

OBJECTIVE: Kommerell diverticulum with aortic dissection involving aortic arch is a rare but troublesome condition. The purpose of this study is to summarize the experience and strategy of surgical treatment. METHOD: From November 2015 to January 2018, seven consecutive patients underwent surgical treatment in our institution. Three patients with acute type A aortic dissection and one patient with acute type B aortic dissection received total arch replacement and frozen elephant trunk (FET) implantation through median sternotomy. Three patients with chronic type B aortic dissection underwent total aortic arch and descending aorta replacement through median sternotomy and lateral thoracotomy. RESULT: There were seven male patients whose median age was 42.3 ± 11.7 (from 14 to 54) years old. There was no perioperative death in this study. One patient had postoperative critical illness polyneuropathy and required prolonged mechanical ventilation (485 hours) and recovered finally. Follow up was completed for all seven patients with a median follow-up time of 7 (3-46) months. One patient with type A dissection developed aneurysm of the descending aorta distal to the FET and received reintervention. No clinical events and abnormal computed tomography manifestations were found in the other seven patients. CONCLUSION: Total arch replacement and FET through single median incision is a reliable method for Kommerell diverticulum associated with acute dissection involving arch. For Kommerell diverticulum associated with chronic type A or B aortic dissection involving aortic arch, graft replacement by double or single incision is safe and appropriate.

[Establishment of a congenital chloride diarrhea-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model and a preliminary analysis of its mechanism of action].

OBJECTIVE: To establish a congenital chloride diarrhea (CCD)-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model, and to investigate its biological function. METHODS: The sequence of the SLC26A3 gene in GenBank was used to design the upstream and downstream single-guide RNA (sgRNA) that could specifically recognize the 392 locus of the SLC26A3 gene, and the sgRNA was mixed with the pSpCas9-puro vector after enzyme digestion to construct an eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3). Caco-2 cells were transfected with the recombinant plasmid and synthesized single-stranded DNA oligonucleotides (ssODNs), and Taqman genotyping assay and Sanger sequencing were used to identify the expression of SLC26A3 c.392C>G (p.P131R) in Caco-2 cells. Wild-type Caco-2 cells were selected as normal control group and the Caco-2 cells with successful expression of SLC26A3 c.392C>G (p.P131R) was selected as P131R group. Both groups were treated with 100 ng/mL tumor necrosis factor-α (TNF-α), and then the normal control group was named as TNF-α group, and the P131R group was named as TNF-α+P131R group. Electric cell-substrate impedance sensing (ECIS) assay was used to evaluate the change in the monolayer barrier function of intestinal epithelial cells in the above four groups, and Western blot was used to measure the change in the expression of SLC26A3 protein in the normal control group and the P131R group. RESULTS: The eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3) was successfully constructed. Both Taqman genotyping assay and Sanger sequencing confirmed the successful establishment of the Caco-2 cell model of SLC26A3 c.392C>G (p.P131R) expression. ECIS assay showed that compared with the normal control group, the P131R group had a significant increase in the monolayer permeability of intestinal epithelial cells (P<0.05), and at the same time, the P131R group had a significantly greater increase in cell membrane permeability after the induction with 100 ng/mL TNF-α (P<0.05). Western blot showed that compared with the normal control group, the P131R group had a significant reduction in the expression of SLC26A3 protein (P=0.001). CONCLUSIONS: SLC26A3 c.392C>G (p.P131R) can reduce the expression of SLC26A3 protein, increase the monolayer permeability of intestinal epithelial cells, and thus lead to diarrhea.

A UPLC-TOF/MS-based metabolomics study of rattan stems of Schisandra chinensis effects on Alzheimer's disease rats model.

A UPLC-TOF/MS-based metabolomics method was established to explore the therapeutic mechanisms of rattan stems of S. chinensis (SCS) in Alzheimer's disease (AD). Experimental AD model was induced by intra-hippocampal Aß1-42 injection in rats. Cognitive function and oxidative stress condition in brain of AD rats were assessed using Morris water maze tests and antioxidant assays [malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)], respectively. UPLC-TOF/MS combined with multivariate statistical analysis were conducted to study the changes in metabolic networks in serum of rats. The results indicated that the AD model was established successfully and the inducement of Aß1-42 caused a decline in spatial learning and memory of rats. The injection of Aß1-42 in rat brains significantly elevated the level of MDA, and reduced SOD and GSH-Px activities. In addition, SCS showed significant anti-AD effects on model rats. A total of 30 metabolites were finally identified as potential biomarkers of AD and 14 of them had a significant recovery compared with the AD model after SCS administration. Changes in AD metabolite profiling were restored to different levels through the regulation of 13 pathways. This is first report on the use of the UPLC-TOF/MS-based serum metabolomics method to investigate therapeutic effects of SCS on AD, and enrich potential biomarkers and metabolic networks of AD.

New Glycosides from the Fruits of Nicandra physaloides.

Three new glycosides (1-3) and 15 known ones (4-18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4-18) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values from 26.9 to 47.5 µM.

Reproductive toxicity in male mice after exposure to high molybdenum and low copper concentrations.

To evaluate the effects of dietary high molybdenum (HMo) and low copper (LCu) concentrations on reproductive toxicity of male mice, 80 mice were divided into 4 groups of 20. These groups were fed with the following: (1) normal control (NC) diet (NC group); (2) NC and HMo diets (HMo group); (3) LCu diet (LCu group); and (4) HMo and LCu diets (HMoLCu group). On the 50th and 100th day, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were analyzed to determine oxidative stress states. Morphological changes in testicular tissue were evaluated with hematoxylin and eosin staining and ultrastructural changes were monitored by transmission electron microscopy. The results showed that administration of HMo, LCu, and HMoLCu not only decreased sperm density and motility but also increased the rate of teratosperm occurrence. A significant increase in MDA content and a decrease in SOD, GSH-Px, and T-AOC contents were observed in LCu, HMo, and HMoLCu groups. Testicular tissues and cells of mice were damaged by HMo and the damages were more serious in the case of Cu deficiency. Exposure to HMo adversely affected the reproductive system of male mice, and dietary LCu plays key roles in HMo-induced reproductive toxicity.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Stratifying risk of failure to achieve textbook outcomes among patients undergoing hepatectomy for hepatocellular carcinoma: A multicenter score validation study.

BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.

Flanged Bentall Plus Cabrol Procedure for Interventricular Septal Dissection in Behçet's Disease.

Behçet's disease with interventricular septal dissection is extremely rare, and its surgical treatment is even more challenging. One such treatment with interventricular septal dissection repair was followed by the flanged Bentall and Cabrol techniques. The flange of the flanged composite graft was attached to the left ventricular outflow tract instead of the fragile annulus. The Cabrol procedure was performed to reduce anastomotic tension at the coronary button sites. Good short-term results were achieved.

Surgical treatment of thoracic aortic pseudoaneurysm caused by Brucella melitensis.

Thoracic aortic pseudoaneurysm caused by Brucella melitensis is extremely rare with extremely few cases reported to date. Herein, we present the case of a 65 year-old man with a huge pseudoaneurysm of the proximal descending thoracic aorta, involving the left subclavian artery and distal arch. Surgery was performed to replace the proximal descending aorta with a self-made bovine pericardial duct and the left subclavian artery with a 10 mm artificial vessel under deep hypothermic circulatory arrest; the patient recovered uneventfully. However, continued follow-up is required for long-term results.

Aplasia cutis congenita in monozygotic twins.

Aplasia cutis congenita (ACC) is defined as complete or partial loss or absence of skin at birth and it can occur on any part of the body, but most commonly on the scalp. Single offspring with ACC have been reported in most case reports, but cases in twins are rarely reported. Here, we report two cases of ACC, monozygotic twin boys presented with scattered skin absence over the scalp vertex after birth. All the lesions presented as ulcers with no hair and healed with scars, otherwise, the twins were well developed mentally and physically. In addition, the whole exome sequencing of the twins and their parents might provide diagnosis and classification assistance.

Clinical outcomes of the cuff wrapping technique in the modified Bentall procedure: a propensity score-matched study.

Background: This study was designed to evaluate the clinical outcomes of our modified cuff wrapping Bentall (M-Bentall) procedure, which uses a cuff wrapping technique with remnant aortic root tissue. Methods: From July 2017 to December 2021, a total of 136 patients met the inclusion criteria for this study. Among them, patients who underwent the modified Bentall procedure using the cuff wrapping technique were included in the M-Bentall group (n=46), while patients who underwent the classic Bentall (C-Bentall) procedure were categorized into the C-Bentall group (n=90). To reduce baseline differences between the two groups, 1:1 nearest-neighbor propensity score matching (PSM) was performed. Demographic and perioperative data were documented and compared between the two groups. Results: Ninety patients were successfully matched (45 pairs). In-hospital mortality was not significantly different between the two groups after PSM (P=1). No differences were found in serious adverse events. The cardiopulmonary bypass (CPB) time was longer in the M-Bentall group than in the C-Bentall group (154 vs. 126 min, P=0.018). The same was also observed for the aortic cross-clamp time (113 vs. 92 min, P=0.009). Postoperatively, the peak value of D-dimer showed a significant difference, with higher values in the C-Bentall group (4.73 vs. 2.89 mg/L, P=0.019). The incidence of postoperative contrast extravasation at the aortic root (P=0.030) was higher in the C-Bentall group. The incidence of persistent aortic-right atrial shunts showed an increased tendency in the C-Bentall group (8.89% vs. 0%, P=0.117). Conclusions: The cuff wrapping technique is a safe and effective method to facilitate hemostasis of the aortic root in the modified Bentall procedure.

Molybdenum-Induced Apoptosis of Splenocytes and Thymocytes and Changes of Peripheral Blood in Sheep.

To investigate the effects of molybdenum (Mo) on apoptosis of lymphocytes and changes of peripheral blood in sheep, a total of 20 5-month-old healthy female sheep were randomly divided into five groups of 4 and orally administered with water containing Na2MoO4·2H2O (0, 5, 10, 20, and 50 mg/kg BW/day) for 28 days. Jugular vein blood was taken on the 0th, 7th, 14th, 21st, and 28th day of Mo treatment, respectively. On the 28th day, the spleen and thymus were removed for observing histopathology and apoptosis-related DNA damage by hematoxylin and eosin (HE) staining and TdT­mediated dUTP Nick-End Labeling (TUNEL) staining, respectively. The blood routine indexes were determined by an automatic blood analyzer. Further, the apoptosis of lymphocytes and changes in mitochondrial membrane potential (MMP) of peripheral blood were analyzed by flow cytometry. Results showed that excessive Mo induced apoptosis-related DNA damage in the splenocytes and thymocytes and significantly increased the apoptosis indexes of the splenocytes and thymocytes (P < 0.01). Furthermore, the treatment with excessive Mo significantly decreased the MMP (P < 0.01) and promoted apoptosis in peripheral blood lymphocytes (P < 0.01). And the number of WBC, Lymph, Gran, and RBC and the indexes of HGB and HCT were also significantly decreased (P < 0.05 or P < 0.01), while RDW was significantly increased by excessive Mo (P < 0.05 or P < 0.01). In conclusion, excessive Mo-induced DNA damage and apoptosis of the lymphocytes changed the RBC-related indexes of the peripheral blood in sheep.

Diclazuril-induced expression of CDK-related kinase 2 in the second-generation merozoites of Eimeria tenella.

Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. Cyclin-dependent kinases (CDK) are prominent target proteins in apicomplexan parasites. In this study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of Eimeria tenella (EtCRK2) were detected. mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. The anticoccidial drug diclazuril against E.tenella affects the expression pattern of EtCRK2 molecule, and EtCRK2 is a potential target for new drug development.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.

Evaluation of aristolochic acid Ι nephrotoxicity in mice via 1H NMR quantitative metabolomics and network pharmacology approaches.

Background: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion: This work provides a meaningful insight for the mechanism of AAΙ renal injury.