KIS, a target of SOX4, regulates the ID1-mediated enhancement of ß-catenin to facilitate lung adenocarcinoma cell proliferation and metastasis.

PURPOSE: Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/ß-catenin pathway. METHODS: Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo. RESULTS: In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the ß-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells. CONCLUSION: KIS, a target of SOX4, regulates the ID1-mediated enhancement of ß-catenin to facilitate LUAD cell invasion and metastasis.

Effect of early cannulation with metal needles on arteriovenous fistula patency in patients undergoing hemodialysis.

BACKGROUND: Autogenous arteriovenous fistula (AVF) is the preferred vascular access mode. However, the earliest possible time for AVF puncture and whether premature puncture affects the AVF patency rate remain unclear. METHODS: In this multicenter retrospective cohort study, adult uremic patients who underwent AVF surgery for the first time at Taizhou Hospital or Enze Hospital of Zhejiang Province between September 1, 2018 and August 31, 2021 were enrolled. All patients were followed up for 1 year after puncture, and the status of fistula establishment and puncture, subsequent patency, loss to follow-up, renal transplantation, conversion to peritoneal dialysis, abandonment of the fistula, and death, were recorded. RESULTS: A total of 465 patients with AVFs were included in this study, including 59 (12.7%) patients with fistulas that were cannulated within 30 days. In the early puncture group, the levels of serum creatinine and urea nitrogen were higher, while the levels of hemoglobin and albumin were lower, suggesting that these patients needed urgent dialysis. Furthermore, the rate of non-cuffed catheter use was higher, while the rate of cuffed catheter use was lower, and femoral vein puncture was preferred over internal jugular vein puncture. The mean duration of catheter indwelling was shorter in the early puncture group (19 vs 70 days, p < 0.001). The estimated AVF primary and cumulative functional patency at 12 months was 81.1% versus 82.3% and 98.3% versus 98.7% in the early puncture and control groups, respectively. Kaplan-Meier analysis revealed no significant difference in AVF primary and cumulative functional patency between the two groups. CONCLUSIONS: In patients with an established fistula in urgent need of hemodialysis, to avoid new catheterization, a puncture can be performed within 30 days in those with well-developed blood vessels after adequate ultrasound and clinical evaluation without affecting the patency of the fistula.

Rapid determination of the relative configuration of diverse 8,4'-oxyneolignans by NMR analysis: Retrospective studies, improvement and structural revision.

The characteristic 1H NMR signals (H-7 and H2-9) are significant parameters that have been widely used to assess the relative configuration of H-7 and H-8 of 8,4'-oxyneolignans. However, many usual 8,4'-oxyneolignans cannot be accurately determined by existing NMR methods and no research considering their limitations was performed until now. In this study, the application scope of NMR methods was comprehensively studied and the ΔδH9a-H9b methods have been extended to solve the majority of configuration determination difficulties. The accuracy of extended NMR methods was verified by anisotropic NMR (RCSA measurements), NMR calculation and diverse statistical analysis (MAEΔΔδ, CP3 and DP4+). Furthermore, the theoretical conformational analysis was performed to investigate the inherent limitations of existing NMR methods. This study could provide a valuable reference for determining the relative configuration of H-7 and H-8 in 8,4'-oxyneolignans and the relative configuration of 23 recently reported 8,4'-oxyneolignan derivatives should be reassigned as well.

Insight into tetrahydrofuran lignans from Isatis indigotica fortune with neuroprotective and acetylcholinesterase inhibitor activity.

Nine tetrahydrofuran lignans, including three undescribed spiro-lignans, were isolated from Isatis indigotica Fortune (Brassicaceae). Extensive spectroscopic analyses achieved the structure elucidation of these tetrahydrofuran lignans, and quantum chemical calculation combined with the MAEΔΔδ parameter. Notably, isatispironeols A-B have a unique spiro[dienone-tetrahydrofuran] molecular core. These spiro[dienone-tetrahydrofuran] lignans showed comparable neuroprotective effects as the positive control in the H2O2-induced SH-SY5Y cells model. In addition, (-)-(7R,8S,1'R,7'R,8'R)-isatispironeol A possessed more significant AChE inhibitory activity, further interact sites were also predicted by the in silico assay.

Systemic lupus erythematosus complicated with Fanconi syndrome: a case report and literature review.

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations. The symptoms of SLE in children are more atypical than adults. Childhood SLE complicated with Fanconi syndrome is extremely rare and even more difficult to diagnose. Case presentation: This article reports a preschool boy with SLE who presented with renal tubular acidosis, accompanied by weakness in both lower limbs, delayed growth, and malnutrition. It was later found that the patient had the complication of Fanconi syndrome with renal tubular acidosis. Ultimately, renal biopsy confirmed lupus nephritis. The patient was treated with corticosteroid combined with mycophenolate mofetil, hydroxychloroquine, and belimumab. The symptoms of the child were relieved. Conclusion: Here we report an extremely rare case of childhood SLE complicated with Fanconi syndrome. There has been no similar clinical report. It is necessary to be alert to the possibility of atypical SLE in children to avoid missed diagnosis and misdiagnosis.

Solanoids F - I: Terpenoids from Solanum lyratum with neuroprotective effects against H2O2-induced SH-SY5Y cell injuries.

Four new terpenoids, solanoids F - I (1-4), together with eleven known compounds (5-15), were isolated from the whole herb of Solanum lyratum. The chemical structures were characterized by spectroscopic techniques, and electronic circular dichroism (ECD) data analysis was adopted to confirm the absolute configurations of 1-4. Compounds 1-6, 8 and 12-15 exhibited neuroprotective effects against H2O2-induced oxidative damage of human SH-SY5Y cells. Additionally, this study also combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore the potential targets and signaling pathways of active terpenoids components in intervening Alzheimer's disease (AD).

The nature compound dehydrocrenatidine exerts potent antihepatocellular carcinoma by destroying mitochondrial complexes in vitro and in vivo.

Cumulative evidence indicates that mitochondria dysfunction plays an important role in tumour treatment. Given the limited efficacy and toxicity of current mitochondria-targeted drugs, research into effective mitochondria-targeted anticancer agents remains an irresistible general trend. In this study, it was found that dehydrocrenatidine (DEC), a ß-carbolin alkaloid isolated from Picrasma quassiodes, displays a promising growth inhibitory effect in vitro and in vivo by inducing apoptosis of hepatocellular carcinoma (HCC) cells. Mechanistically, we provided that the possible target of DEC against HCC cells was determined by isobaric labels for relative and absolute quantification assay and validated them using further experiments. The results suggested that DEC can target and regulate the function of mitochondrial complexes I, III and IV, affecting oxidative phosphorylation and ultimately leading to mitochondrial dysfunction to exert its anti-HCC effects. In addition, the combination of DEC and sorafenib showed a synergistic effect and was also associated with mitochondrial dysfunction. Importantly, DEC did not show significant toxicity in mice. This study provided a new insight into underlying mechanisms in DEC-treated HCC cells, suggesting that DEC might be a mitochondrial targeting lead compound.

Discovery of alkaloids from the leaves of Isatis indigotica Fortune with neuroprotective activity.

Seven alkaloids including five undescribed ones (1a/1b, 2, 3 and 5) were obtained from the leaves of Isatis indigotica Fortune. Their structures were established by extensive spectroscopic analyses. The absolute configurations of compounds 1a, 1b, 3 and 5 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Subsequently, the neuroprotective effects of all the isolates against H2O2-induced injury in SH-SY5Y cells were evaluated in vitro by MTT assay. Moreover, Annexin V-FITC/PI double staining was performed, while the activities of antioxidant enzymes (SOD, CAT and GSH-Px) for compounds 1a and 1b were measured.

A new dineolignan with anti-ß-amyloid aggregation activity from the fruits of crataegus pinnatifida bge.

A new dineolignan, crataeguslignan A (1), along with one known dineolignan (2) were isolated from the fruits of Crataegus pinnatifida Bge. Its chemical structure was identified by comprehensive spectroscopic analyses. All the isolated compounds were investigated with regard to their Aß1-42 inhibition activity. Among them, 1 displayed the most potent Aß1-42 inhibitory ability with the inhibition rate of 85.2% at the concentration of 20 µM.

[Association of age distribution with the expression of angiotensin-converting enzyme 2 in lung tissues in severe acute respiratory syndrome coronavirus 2 infection: reflections from the study of RAS pathway expression in mice].

OBJECTIVE: To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. METHODS: The mice at different developmental stages were enrolled, including fetal mice (embryonic days 14.5 and 18.5), neonatal mice (0, 3, 7, 14, and 21 days old), young mice (28 and 42 days old), and adult mice (84 days old). The lung tissues of all fetal mice from 4 pregnant mice were collected at each time point in the fetal group. Four mice were sampled in other age groups at each time point. Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. RESULTS: The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. It increased gradually after birth, reached a peak on day 3 after birth, and reached a nadir on day 14 after birth (P<0.05). The expression of AGT reached a peak on days 0 and 7 after birth and reached a nadir on day 21 after birth (P<0.05). The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). Agtr1a expression reached a peak on day 21 after birth (P<0.05). Agtr2 expression gradually decreased to a low level after birth. Renin, Agtr1b, and Mas1 showed low expression in lung tissues at all developmental stages. CONCLUSIONS: At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. The other key molecules of the RAS pathway have their own expression patterns. These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.

Xanthatin alleviates airway inflammation in asthmatic mice by regulating the STAT3/NF-κB signaling pathway.

Here, we aimed to investigate the role of Xanthatin in asthma and its underlying mechanism. BALB/c mice were treated with ovalbumin (OVA) to establis a mouse model of asthma. Our results showed that OVA injection significantly increased inflammatory cell infiltration and goblet cell hyperplasia in lung issues, while Xanthatin treatment and STAT3 inhibitor C188-9 administration relieved these symptoms. Moreover, OVA-induced OVA-specific immunoglobulin E level in serum and the number of total cell, macrophages, lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid (BALF) were markedly reduced by Xanthatin treatment and signal transducer and activator of transcription 3 (STAT3) inhibition. Additionally, Xanthatin treatment and STAT3 inhibition was also significantly decreased the levels of inflammatory cytokines in BALF in asthmatic mice. We further demonstrated that the STAT3/nuclear factor-kappaB (NF-κB) pathway was blocked by Xanthatin in asthmatic mice. Overall, we conclude that Xanthatin attenuates airway inflammation in asthmatic mice through blocking the STAT3/NFκB signaling pathway, indicating the potential of Xanthatin as a useful therapeutic agent for asthma.

MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer.

BACKGROUND: Cervical cancer is one of the most common cancers among females worldwide and advanced patients have extremely poor prognosis. However, adverse reactions and accumulating resistance to radiation therapy require further investigation. METHODS: The expression levels of mitogen-activated protein kinase 4 (MAPK4) mRNA were analyzed by real-time PCR and its association with overall survival was analyzed using Kaplan-Mier method. Colony formation, immunofluorescence and western blotting were used to examine the effects of MAPK4 knockout or over-expression on cervical cancer cells after radiation treatment. Drug-sensitivity of cervical cancer cells to PARP1 inhibitors, olaparib or veliparib, was analyzed by CCK-8 cell viability assays, and the 50% inhibitory concentration (IC50) was quantified using GraphPad Prism. The functional effects of MAPK4 knockout on the sensitivity of cervical cancer to radiation treatment and PARP1 inhibitors were further examined using xenograft tumor mouse models in vivo. RESULTS: Cervical cancer patients with high MAPK4 mRNA expression have lower survival rate. After radiation treatment, the colony number of MAPK4 knockout cells was markedly reduced, and the markers for DNA double-chain breakage were significantly up-regulated. In addition, MAPK4 knockout reduced protein kinase B (AKT) phosphorylation, whereas its over-expression resulted in opposite effects. In MAPK4 KO cells with irradiation treatment, inhibition of AKT phosphorylation promoted DNA double-chain breakage. Constitutive activation of AKT (CA-AKT) increased the levels of phosphorylated-AKT (p-AKT), and DNA repair-related proteins, phosphorylated-DNA-dependent protein kinase (p-DNA-PK) and RAD51 recombinase (RAD51). Furthermore, MAPK4 knockout was found to affect the sensitivity of cervical cancer cells to poly ADP-ribose polymerase 1 (PARP1) inhibitors by activating the phosphorylation of AKT. Moreover, in vivo results demonstrated that MAPK4 knockout enhanced the sensitivity of cervical cancer to radiation and PARP1 inhibitors in mouse xenograft models. CONCLUSIONS: Collectively, our data suggest that combined application of MAPK4 knockout and PARP1 inhibition can be used as therapeutic strategy in radiation treatment for advanced cervical carcinoma.

The clinical efficiency of lycium-rehmannia pills in treating dry eye symptom: A meta-analysis.

BACKGROUND: Dry eye symptom threatens human health and causes a larger burden of disease, the study aims to systematically compare the therapeutic effect of Lycium-rehmannia pills combined with topical eye drops and pure western medicine (western medicine eye drops) on dry eye symptom, to provide a reflection and enlightenment for clinical treatment. METHOD: PubMed, The Cochrane Library, EMbase, MEDLINE, CBM, WanFang, VIP, and CNKI databases were searched manually and automatically by the computer until March 2019 and relevant randomized controlled trials (RCTs) were selected. Article selection and data extraction were conducted by 2 researchers independently, then RevMan 5.3 was applied for meta-analysis. RESULT: Fifteen randomized controlled trials were included, including 1222 patients (eyes = 2382). The meta-analysis results showed that Lycium-rehmannia pills combined with western medicine were superior to the control group in terms of therapeutic efficiency [OR = 4.38, 95% confidence interval (CI) (3.26, 5.89), P < .00001]. There were controversial results that the study group was better than the control group in Basic Schirmer test [MD, 2.46, 95% CI (1.49, 3.44), P < .00001], tear break up time [MD, 3.79, 95% CI (3.57, 4.01), P < .00001], and Fluorescein test [MD, -1.29, 95% CI (-1.42, -1.15), P < .00001], but Lycium-rehmannia pills combined with western medicine could not reduce the incidence of adverse reactions, including eyelid inflammation [OR = 1.00, 95% CI (0.37, 2.72), P = 1.00] and congestion symptom [OR = 0.55, 95% CI (0.18, 1.65), P = .28]. CONCLUSION: Lycium-rehmannia pills combined with western medicine is better than the control group of therapeutic efficiency in the treatment of dry eye symptom. Due to the quantity and quality limitations of the literature, there were controversial results that the study group was better than the control group in Basic Schirmer test, Tear break up time, Fluorescein test, and reduced adverse reactions, including inflammation of the eyelids and congestion. The above conclusion needs more clinical trials to test and verify.

Allogeneic hematopoietic stem cell transplantation for Crohn disease complicated with myelodysplastic syndrome: A case report.

RATIONALE: Myelodysplastic syndrome (MDS) can be complicated with Crohn disease (CD). Irritable bowel disease (IBD) associated with MDS has already been reported in the past; however, hematopoietic stem cell transplantation (HSCT) is rarely performed. Herein, we report a case of CD with MDS for HSCT. PATIENT CONCERNS: A 41-year-old man was hospitalized due to abdominal pain and intermittent fever for 40 days. Two years later, he was readmitted due to abdominal pain and diarrhea with fever for 10 days. DIAGNOSIS: Symptoms, laboratory examinations, and imaging findings of the patient were indicative of CD complicated with MDS. INTERVENTIONS: An allogeneic HSCT was performed. OUTCOMES: He died of severe lung infection 125 days post-transplantation. LESSONS: The number of cases of CD combined with MDS remains insufficient, and no consensus opinions are available to date. Hence, HSCT is a very potential treatment method. Additional experiences are needed to determine its effectiveness.

Four pairs of alkaloid enantiomers from Isatis indigotica Fortune Ex Land with neuroprotective effects against H2O2-induced SH-SY5Y cell injury.

In the current study, four pairs of new enantiomeric alkaloids (1a/1b-4a/4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively.

MiRNA-192-5p attenuates airway remodeling and autophagy in asthma by targeting MMP-16 and ATG7.

Asthma is a chronic lung inflammatory disease with high incidence. MicroRNA-192-5p (miR-192-5p) was down-regulated in asthmatics. However, the role of miR-192-5p in asthma is still unclear. In current study, in vitro, the overexpression of miR-192-5p, matrix metalloproteinase (MMP)-16 and autophagy related 7 (ATG7) was conducted in airway smooth muscle cells (ASMCs). We found that miR-192-5p suppressed cell proliferation, and decreased MMP-16 and ATG7 expression. MMP-16 and ATG7 promoted cell proliferation, and further alleviated the down-regulation of miR-192-5p on proliferation of ASMCs. in vivo, miR-192-5p was down-regulated in asthma mice, and involved in improvement of asthma mice. MiR-192-5p was demonstrated to alleviate inflammation in asthma mice, including decreasing the level of ovalbumin (OVA)-specific IgE, interleukin (IL)-4, IL-5, IL-13, iNOS and COX-2. Moreover, the attenuation of airway remodeling induced by miR-192-5p in asthma mice were expressed by the reduction of fibroblast growth factor-23 (FGF-23) level, decrease in concentrations of MMP-2 and MMP-9 as well as down-regulation of collagen I deposition. Further, miR-192-5p also caused the suppression of autophagy in asthma mice, exhibiting a decrease in LC3II/I, beclin-1 and ATG7, and an increase in p62. Importantly, MMP-16 and ATG7 were confirmed to be targets of miR-192-5p. Therefore, our results indicate that miRNA-192-5p may attenuate airway remodeling and autophagy in asthma via targeting MMP-16 and ATG7.

miR-363-3p inhibits migration, invasion, and epithelial-mesenchymal transition by targeting NEDD9 and SOX4 in non-small-cell lung cancer.

miR-363-3p is downregulated in lung adenocarcinoma and can inhibit tumor growth. Here, we aimed to investigate the effect of miR-363-3p on non-small-cell lung cancer (NSCLC) metastasis. In our study, miR-363-3p overexpression inhibited cell migration and invasion via epithelial-mesenchymal transition inhibition, while miR-363-3p knockdown exhibited the opposite effects. Further studies demonstrated that miR-363-3p bound to 3'-untranslated regions of NEDD9 and SOX4, and negatively regulated their levels. Interestingly, NEDD9 or SOX4 knockdown rescued the metastasis-promoting effects of antagomiR-363-3p. The inhibitory effects of agomiR-363-3p were also blocked by NEDD9 or SOX4 overexpression. Moreover, lentivirus particles carrying pre-miR-363 (LV-pre-miR-363) significantly decreased, while LV-miR-363-3p inhibitor increased metastatic nodule numbers and the levels of NEDD9 and SOX4 in lungs. In conclusion, tumor suppressor miR-363-3p may be a potential target in NSCLC therapy.

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury.

Six pairs of alkaloid enantiomers including 11 new alkaloids (1A: /1B: -5A: /5B, 6A: ) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5A/5B: and 6A/6B: exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.

Diverse metabolites from corn silk with anti-Aß1-42 aggregation activity.

Five pairs of enantiomeric compounds (1a/1b-5a/5b) including seven undescribed compounds (1a/1b-3a/3b, 4b) along with two known ones (. and .) have been isolated from corn silk (Stigma maydis). Racemic mixtures of these enantiomers were separated by HPLC with different types of chiral columns. Their structures were elucidated based on comprehensive spectroscopic analyses together with quantum chemical calculations of 13C NMR data and electronic circular dichroism (ECD) curves. All the isolates were evaluated for their inhibition ability of self-induced Aß1-42 aggregation. Among them, compounds 4a (88.36%), 4b (74.66%) and . (85.65%) showed stronger inhibitory activity than the positive control curcumin (61.90%). The different inhibition profiles of enantiomers 4a and 4b were explained by docking simulation studies.