Merging total synthesis and NMR technology for deciphering the realistic structure of natural 2,6-dideoxyglycosides.

The structural identification and efficient synthesis of bioactive 2,6-dideoxyglycosides are daunting challenges. Here, we report the total synthesis and structural revision of a series of 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx, which feature pregnane steroidal aglycones bearing an 18,20-lactone and glycans consisting of 2,6-dideoxy-3-O-methyl-ß-pyranose residues, including ecdysosides A, B, and F and ecdysantheroside A. All the eight possible 2,6-dideoxy-3-O-methyl-ß-pyranoside stereoisomers (of the proposed ecdysantheroside A) have been synthesized that testify the effective gold(I)-catalyzed glycosylation methods for the synthesis of various 2-deoxy-ß-pyranosidic linkages and lays a foundation via nuclear magnetic resonance data mapping to identify these sugar units which occur promiscuously in the present and other natural glycosides. Moreover, some synthetic natural compounds and their isomers have shown promising anticancer, immunosuppressive, anti-inflammatory, and anti-Zika virus activities.

Selenium in the treatment of mild-to-moderate Graves' orbitopathy: a 5-year prospective controlled cohort study.

PURPOSE: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO. METHODS: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL. RESULTS: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01). CONCLUSION: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.

Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein.

BACKGROUND: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. PURPOSE: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. METHODS: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RT-qPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the anti-ZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. RESULTS: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-of-addition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. CONCLUSION: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources.

Pectic oligosaccharides ameliorate high-fat diet-induced obesity and hepatic steatosis in association with modulating gut microbiota in mice.

Accumulating evidence has shown that gut microbiota and its metabolites have important significance in the etiology of obesity and related disorders. Prebiotics prevent and alleviate obesity by modulating the gut microbiota. However, how pectin oligosaccharides (POS) derived from pectin degradation affect gut microbiota and obesity remains unclear. To investigate the potential anti-obesity effects of POS, mice were fed a high-fat diet (HFD) for 12 weeks and a POS supplement with drinking water during the last 8 weeks. The outcomes demonstrated that POS supplementation in HFD-fed mice decreased body weight (P < 0.01), improved glucose tolerance (P < 0.001), reduced fat accumulation (P < 0.0001) and hepatic steatosis, protected intestinal barrier, and reduced pro-inflammatory cytokine levels. After fecal metagenomic sequencing, the POS corrected the gut microbiota dysbiosis caused by the HFD, as shown by the increased populations of Bifidobacterium, Lactobacillus taiwanensis, and Bifidobacterium animalis, and decreased populations of Alistipes and Erysipelatoclostridium, which were previously considered harmful bacteria. Notably, the changed gut microbiota was associated with the obesity prevention of POS. These findings demonstrate that POS regulates particular gut microbiota, which is essential owing to its ability to prevent disorders associated with obesity.

Efficacy and safety of combined Chinese and Western medicine in the treatment of knee osteoarthritis: a prospective, multicenter cohort study.

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).

Impact of Prior Cancer on the Prognosis of Patients with Chondrosarcoma: A Population-Based Study of the SEER Database.

Background: Patients with prior cancer are generally exempt from cancer experiments. This research aims to describe the prevalence, clinical features, and effects of past malignancy among patients with chondrosarcoma. Methods: Chondrosarcoma patients diagnosed between 2010 to 2015 were collected from the SEER database. The propensity score matching method was used to reconcile the disparity in baseline attributes. Kaplan-Meier analysis was employed to explore the outcomes of prior cancer on overall survival. The proportional hazards assumption was used to certain whether the covariate matched the Cox regression model. The potential outliers were estimated by deviance residuals type. Results: A total of 1,721 unique individuals were collected, of those 284 (16.50%) patients had a history of cancer, with prostate cancer being commonly documented (n = 49, 17.25%). Approximately half of the previous tumors are diagnosed within 5 years before the diagnosis of chondrosarcoma. Chondrosarcoma patients with prior cancers have a lower survival rate than those without prior malignancy (P < .001). A multivariable Cox analysis reveals that past cancer is a distinct risk factor for lifespan (hazard ratio = 2.489, P < .001). Conclusion: This study initially discovered that chondrosarcoma patients with past cancer have a bad prognosis. Different types of past cancer have varying effects on survival. We urgently propose that cancer trial exclusion criteria be set specifically by cancer classification, rather than accepting the unchangeable criterion for default.

Angelica sinensis polysaccharide ameliorates nonalcoholic fatty liver disease via restoring estrogen-related receptor α expression in liver.

Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 107 vs. 2.13 ± 0.52 × 107 ) and butyrate (1.83 ± 1.31 × 107 vs. 6.39 ± 1.44 × 107 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine-choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.

Paeonol repurposing for cancer therapy: From mechanism to clinical translation.

Paeonol (PAE) is a natural phenolic monomer isolated from the root bark of Paeonia suffruticosa that has been widely used in the clinical treatment of some inflammatory-related diseases and cardiovascular diseases. Much preclinical evidence has demonstrated that PAE not only exhibits a broad spectrum of anticancer effects by inhibiting cell proliferation, invasion and migration and inducing cell apoptosis and cycle arrest through multiple molecular pathways, but also shows excellent performance in improving cancer drug sensitivity, reversing chemoresistance and reducing the toxic side effects of anticancer drugs. However, studies indicate that PAE has the characteristics of poor stability, low bioavailability and short half-life, which makes the effective dose of PAE in many cancers usually high and greatly limits its clinical translation. Fortunately, nanomaterials and derivatives are being developed to ameliorate PAE's shortcomings. This review aims to systematically cover the anticancer advances of PAE in pharmacology, pharmacokinetics, nano delivery systems and derivatives, to provide researchers with the latest and comprehensive information, and to point out the limitations of current studies and areas that need to be strengthened in future studies. We believe this work will be beneficial for further exploration and repurposing of this natural compound as a new clinical anticancer drug.

Efficacy and Safety Evaluation of Bilateral Pedicle Approach Combined with Positional Reduction for the Treatment of Osteoporotic Thoracolumbar Burst Fractures.

Background: Osteoporotic thoracolumbar burst fractures (OTLBF) pose challenges for vertebroplasty due to the risk of cement leakage and spinal injury resulting from the fracture of the posterior vertebra and spinal canal occupancy. It limits the application of vertebroplasty in these patients. Objective: This study investigates the efficacy and safety of a bilateral pedicle approach combined with postural reduction for treating OTLBF using vertebroplasty. Material and Methods: Thirteen patients (aged ≥ 65 years) with thoracolumbar fractures without neurological deficits underwent vertebroplasty. The fractures affected the anterior and middle columns of the vertebrae, with mild compression of the canal. Clinical symptoms, procedure effects, patient mobility, and pain were assessed before the procedure and between 1 day and 3 months post-procedure. Kyphosis correction, wedge angle, and height restoration were also measured. Results: Immediate improvements in pain and mobility were observed in all patients following vertebroplasty, with sustained improvements over 6 months. Significant improvements were observed between 1 day and 6 months post-procedure, with at least a 4-level reduction in pain after 6 months. No comorbidities were observed. Kyphosis correction, wedge angle, and height restoration were improved. In one patient, postoperative computed tomography revealed polymethylmethacrylate leakage into the disc space and paravertebral space through the endplate fracture site, while no intraspinal leakage was found in other patients. Conclusions: Although vertebroplasty is generally considered contraindicated in OTLBF patients with posterior body involvement, this study demonstrates successful and safe treatment without causing neurological deficits. Percutaneous vertebroplasty combined with body reduction may serve as an alternative method for treating OTLBF, effectively preventing major surgical complications. Furthermore, it offers superior kyphosis correction, vertebral body reduction, pain reduction, early mobilization, and pain relief for patients.

WRINKLED1 Positively Regulates Oil Biosynthesis in Carya cathayensis.

Hickory (Carya cathayensis Sarg.) is a kind of important woody oil tree species, and its nut has high nutritional value. Previous gene coexpression analysis showed that WRINKLED1 (WRI1) may be a core regulator during embryo oil accumulation in hickory. However, its specific regulatory mechanism on hickory oil biosynthesis has not been investigated. Herein, two hickory orthologs of WRI1 (CcWRI1A and CcWRI1B) containing two AP2 domains with AW-box binding sites and three intrinsically disordered regions (IDRs) but lacking the PEST motif in the C-terminus were characterized. They are nucleus-located and have self-activated ability. The expression of these two genes was tissue-specific and relatively high in the developing embryo. Notably, CcWRI1A and CcWRI1B can restore the low oil content, shrinkage phenotype, composition of fatty acid, and expression of oil biosynthesis pathway genes of Arabidopsis wri1-1 mutant seeds. Additionally, CcWRI1A/B were shown to modulate the expression of some fatty acid biosynthesis genes in the transient expression system of nonseed tissues. Transcriptional activation analysis further indicated that CcWRI1s directly activated the expression of SUCROSE SYNTHASE2 (SUS2), PYRUVATE KINASE ß SUBUNIT 1 (PKP-ß1), and BIOTIN CARBOXYL CARRIER PROTEIN2 (BCCP2) involved in oil biosynthesis. These results suggest that CcWRI1s can promote oil synthesis by upregulating some late glycolysis- and fatty acid biosynthesis-related genes. This work reveals the positive function of CcWRI1s in oil accumulation and provides a potential target for improving plant oil by bioengineering technology.

The pharmacokinetics profiles, pharmacological properties, and toxicological risks of dehydroevodiamine: A review.

Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from Evodiae Fructus (EF, Wuzhuyu in Chinese, Rutaceae family), a well-known traditional Chinese medicine (TCM) which is clinically applied to treat headache, abdominal pain, menstrual pain, abdominal distension, vomiting, acid regurgitation, etc. Modern research demonstrates that DHE is one of the main components of EF. In recent years, DHE has received extensive attention due to its various pharmacological activities. This review is the first to comprehensively summarize the current studies on pharmacokinetics profiles, pharmacological properties, and toxicological risks of DHE in diverse diseases. Pharmacokinetic studies have shown that DHE has a relatively good oral absorption effect in the mean concentration curves in rat plasma and high absorption in the gastrointestinal tract. In addition, distribution re-absorption and enterohepatic circulation may lead to multiple blood concentration peaks of DHE in rat plasma. DHE possesses a wide spectrum of pharmacological properties in the central nervous system, cardiovascular system, and digestive system. Moreover, DHE has anti-inflammatory effects via downregulating pro-inflammatory cytokines and inflammatory mediators. Given the favorable pharmacological activity, DHE is expected to be a potential drug candidate for the treatment of Alzheimer's disease, chronic stress, amnesia, chronic atrophic gastritis, gastric ulcers, and rheumatoid arthritis. In addition, toxicity studies have suggested that DHE has proarrhythmic effects and can impair bile acid homeostasis without causing hepatotoxicity. However, further rigorous and well-designed studies are needed to elucidate the pharmacokinetics, pharmacological effects, potential biological mechanisms, and toxicity of DHE.

A mechanistic review of chinese medicine polyphenols on bone formation and resorption.

Bone reconstruction includes a steady state system of bone formation and bone absorption. This tight coupling requires subtle coordination between osteoblasts and osteoclasts. If this balance is broken, it will lead to bone mass loss, bone density reduction, and bone metabolic diseases, such as osteoporosis. Polyphenols in Chinese herbal medicines are active ingredients in plant extracts with high safety and few side effects, and they can play a role in affecting bone formation and bone resorption. Some of these have estrogen-like effects and can better target bone health in postmenopausal women. The purpose of this review is to provide comprehensive information on the mechanisms underlying the relationship between traditional Chinese medicine polyphenols and bone formation or bone resorption.

Effect of aerobic exercise on limb motor function in diabetic patients / Efeito do exercício aeróbico sobre a função motora dos membros em pacientes diabéticos / Efecto del ejercicio aeróbico en la función motora de las extremidades en pacientes diabéticos

ABSTRACT Introduction: Gestational Diabetes is a group of metabolic disorders that result in glucose intolerance during pregnancy. Among the range of treatments are diet, continuous use of medication, and psychological monitoring. Since it is a multidisciplinary treatment, a proper protocol is vital for a favorable outcome. In addition, there are questions about the benefits of physical activity as a complementary therapy. Objective: To verify the impact of adding exercise to the hospital protocol for patients with gestational diabetes, both on the risks of type 2 diabetes in pregnant women and on the obesity of their offspring. Methods: Sixty pregnant women diagnosed with Gestational Diabetes were randomly divided into control and intervention groups. Both groups received specific treatment and intervention, and the experimental group practiced controlled moderate-intensity physical activity (125-146bpm). Morning blood samples were collected from both groups to check fasting glucose and insulin levels, indicators of lipid metabolism, low and high-density lipoprotein cholesterol, apolipoprotein B. The Brog scale measured the fatigue level. In addition, the premature rupture of membranes, postpartum hemorrhage, neonatal asphyxia, macrosomia, and others was checked. Results: The peripheral blood total cholesterol levels were 5.93, 5. 38, low-density lipoprotein cholesterol levels were 2.95 before versus 2.64 after, and apolipoprotein B levels were 1.84 versus 1.59 in the control group, high-density lipoprotein cholesterol content increased from 1.74 to 1.88, blood cholesterol, and apolipoprotein B levels after the intervention in the experimental group were lower than those in the control group, with an elevation of high-density lipoprotein cholesterol. Conclusion: Aerobic exercise proved to be more appropriate for patients with gestational diabetes in the later stages of pregnancy and may also be adapted for bedridden patients refractory to traditional drugs. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução: O Diabetes Gestacional é um grupo de desordens metabólicas que resultam na intolerância à glicose durante a gravidez, dentre o leque de tratamentos está a dieta, o uso continuo de medicamentos, e acompanhamento psicológico. Por ser um tratamento multidisciplinar, é importante que haja um protocolo adequado para um desfecho favorável. Há questionamentos quanto aos benefícios de atividades físicas como terapia complementar. Objetivo: Verificar o impacto da adição de exercícios ao protocolo hospitalar para pacientes com diabetes gestacional, tanto nos riscos de diabetes tipo 2 em grávidas quanto na obesidade de seus descendentes. Métodos: Sessenta mulheres grávidas que foram diagnosticadas com Diabetes Gestacional foram aleatoriamente divididas em grupos controle e intervenção. Ambos grupos receberam tratamento e intervenção específicos e o grupo experimental praticou atividade física de intensidade moderada controlada (125-146bpm). Amostras de sangue em jejum matinal foram coletados em ambos os grupos para verificar níveis de glicose e insulina em jejum, indicadores de metabolismo lipídico, colesterol lipoproteico de baixa e alta densidade, apolipoproteína B. Verificou-se também o nível de fadiga pela escala Brog, ruptura prematura de bolsa, hemorragia pós-parto, asfixia neo-natal, macrossomia entre outros. Resultados: Os níveis de colesterol total no sangue periférico foram de 5,93, 5.38, os níveis de colesterol lipoproteico de baixa densidade foram 2,95 antes contra 2,64 depois e os níveis de apolipoproteína B foram 1,84 contra 1,59 no grupo controle, o conteúdo de colesterol lipoproteico de alta densidade aumentou de 1,74 para 1,88, os níveis de colesterol, e apolipoproteína B sanguíneos depois da intervenção no grupo experimental foram menores que os do grupo controle, com elevação do colesterol lipoprotéico de alta densidade. Conclusão: O exercício aeróbico mostrou-se mais adequado para pacientes com diabetes gestacional nos estágios posteriores da gravidez, podendo ser adaptado inclusive para as pacientes acamadas refratárias aos fármacos tradicionais. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

Resumen Introducción: La diabetes gestacional es un grupo de trastornos metabólicos que dan lugar a una intolerancia a la glucosa durante el embarazo. Entre la gama de tratamientos se encuentra la dieta, el uso continuado de medicamentos y el seguimiento psicológico. Al tratarse de un tratamiento multidisciplinar, es importante contar con un protocolo adecuado para obtener un resultado favorable. Existen dudas sobre los beneficios de la actividad física como terapia complementaria. Objetivo: Comprobar el impacto de añadir el ejercicio al protocolo hospitalario para pacientes con diabetes gestacional, tanto en los riesgos de diabetes tipo 2 en las mujeres embarazadas como en la obesidad de su descendencia. Métodos: Sesenta mujeres embarazadas a las que se les diagnosticó diabetes gestacional fueron divididas aleatoriamente en grupos de control y de intervención. Ambos grupos recibieron un tratamiento y una intervención específicos y el grupo experimental practicó una actividad física controlada de intensidad moderada (125-146bpm). Se tomaron muestras de sangre en ayunas por la mañana de ambos grupos para comprobar los niveles de glucosa e insulina en ayunas, los indicadores del metabolismo de los lípidos, el colesterol de lipoproteínas de baja y alta densidad, la apolipoproteína B. También se comprobó el nivel de fatiga según la escala de Brog, la rotura prematura de bolsa, la hemorragia posparto, la asfixia neonatal y la macrosomía, entre otros. Resultados: Los niveles de colesterol total en sangre periférica fueron de 5,93, 5. 38, los niveles de colesterol de lipoproteínas de baja densidad eran de 2,95 antes frente a 2,64 después y los niveles de apolipoproteína B eran de 1,84 frente a 1,59 en el grupo de control, el contenido de colesterol de lipoproteínas de alta densidad aumentó de 1,74 a 1,88, el colesterol en sangre y los niveles de apolipoproteína B después de la intervención en el grupo experimental fueron inferiores a los del grupo de control, con una elevación del colesterol de lipoproteínas de alta densidad. Conclusión: El ejercicio aeróbico resultó ser más apropiado para las pacientes con diabetes gestacional en las últimas fases del embarazo, y puede adaptarse incluso a las pacientes encamadas y refractarias a los fármacos tradicionales. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Comparison of the efficiency and microbial mechanisms of chemical- and bio-surfactants in remediation of petroleum hydrocarbon.

Surfactant-enhanced remediation (SER) is one of the most effective methods for petroleum hydrocarbon-contaminated sites compared to single physical and chemical methods. However, biosurfactants are not as commonly used as chemical surfactants, and the actual remediation effects and related mechanisms remain undefined. Therefore, to comprehensively compare the remediation effects and biological mechanisms of biosurfactants and chemical surfactants, soil column leaching experiments including two biosurfactants (rhamnolipids and lipopeptide) and three commercially used chemical surfactants (Tween 80, Triton X-100, and Berol 226SA) were conducted. After seven days of leaching, rhamnolipids exhibited the highest petroleum hydrocarbon removal rate of 61.01%, which was superior to that of chemical surfactants (11.73-18.75%) in n-alkanes C10-C30. Meanwhile, rhamnolipids exhibited a great degradation advantage of n-alkanes C13-C28, which was 1.22-30.55 times that of chemical surfactants. Compared to chemical surfactants, biosurfactants significantly upregulated the soil's biological functions, including soil conductivity (80.90-155.56%), and soil enzyme activities of lipase (90.31-497.10%), dehydrogenase (325.00-655.56%), core enzyme activities of petroleum hydrocarbon degradation, and quorum sensing between species. Biosurfactants significantly changed the composition of Pseudomonas, Citrobacter, Acidobacteriota, and Enterobacter at the genus level. Meanwhile, chemical surfactants had less influence on the bacterial community and interactions between species. Moreover, the biosurfactants enhanced the microbial interactions and centrality of petroleum hydrocarbon degraders in the community based on the network. Overall, this work provides a systematic comparison and understanding of the chemical- and bio-surfactants used in bioremediation. In the future, we intend to apply biosurfactants to practical petroleum hydrocarbon-contaminated fields to observe realistic remediation effects and compare their functional mechanisms.

Preventive effect of pectic oligosaccharides on acute colitis model mice: modulating epithelial barrier, gut microbiota and Treg/Th17 balance.

Pectin as a dietary fiber supplement has shown emerging potential in clinical ulcerative colitis (UC) adjuvant therapy. In this study, the preventive and prebiotic effects of enzymatically degraded pectic oligosaccharides (POS) were further explored in dextran sodium sulfate (DSS)-induced colitis mice. The POS supplement (400 mg kg-1) was significantly effective at improving preventive efficacy, promoting colonic epithelial barrier integrity and reducing inflammatory cytokines. Meanwhile, the changes in T regulatory (Treg) cells and T helper 17 (Th17) cells indicated that POS treatment regulated the Treg/Th17 balance. Gut microbiota analysis showed that the POS supplement reshaped the dysfunctional gut microbiota. Further Spearman's correlation coefficient analysis indicated that the changes of the gut microbiota were highly associated with modulating the epithelial barrier, promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. All of these results suggest that enzymatically- degraded POS is a promising therapeutic agent for UC prevention and adjuvant treatment by maintaining intestinal homeostasis.

Vicious LQT induced by a combination of factors different from hERG inhibition.

Clinically, drug-induced torsades de pointes (TdP) are rare events, whereas the reduction of the human ether-à-go-go-related gene (hERG) current is common. In this study, we aimed to explore the specific factors that contribute to the deterioration of hERG inhibition into malignant ventricular arrhythmias. Cisapride, a drug removed from the market because it caused long QT (LQT) syndrome and torsade de pointes (TdP), was used to induce hERG inhibition. The effects of cisapride on the hERG current were evaluated using a whole-cell patch clamp. Based on the dose-response curve of cisapride, models of its effects at different doses (10, 100, and 1,000 nM) on guinea pig heart in vitro were established. The effects of cisapride on electrocardiogram (ECG) signals and QT interval changes in the guinea pigs were then comprehensively evaluated by multi-channel electrical mapping and high-resolution fluorescence mapping, and changes in the action potential were simultaneously detected. Cisapride dose-dependently inhibited the hERG current with a half inhibitory concentration (IC50) of 32.63 ± 3.71 nM. The complete hERG suppression by a high dose of cisapride (1,000 nM) prolonged the action potential duration (APD), but not early after depolarizations (EADs) and TdP occurred. With 1 µM cisapride and lower Mg2+/K+, the APD exhibited triangulation, dispersion, and instability. VT was induced in two of 12 guinea pig hearts. Furthermore, the combined administration of isoproterenol was not therapeutic and increased susceptibility to ventricular fibrillation (VF) development. hERG inhibition alone led to QT and ERP prolongation and exerted an anti-arrhythmic effect. However, after the combination with low concentrations of magnesium and potassium, the prolonged action potential became unstable, triangular, and dispersed, and VT was easy to induce. The combination of catecholamines shortened the APD, but triangulation and dispersion still existed. At this time, VF was easily induced and sustained.

Chrono-moxibustion adjusts circadian rhythm of CLOCK and BMAL1 in adjuvant-induced arthritic rats.

OBJECTIVE: The clinical symptoms of rheumatoid arthritis (RA) have significant circadian rhythms, with morning stiffness and joint pain. Moxibustion is effective in the treatment of RA, while the underlying therapeutic mechanisms remain limited. Thus, we explored whether moxibustion could adjust the circadian rhythm of RA by modulating the core clock genes CLOCK and BMAL1 at the molecular level. METHODS: 144 Sprague Dawley rats were randomly divided into four groups: control group (group A), model group (group B), 7-9 am moxibustion treatment group (group C), and 5-7 pm moxibustion treatment group (group D). Each group was divided into 6 time points (0 am, 4 am, 8 am, 12 N, 6 pm, and 8 pm) with an equal number of rats at each time point. Except for group A, all rats were injected with Freund's Complete Adjuvant (FCA) 0.15 ml on the right foot pad to establish the RA model. The rats of the two moxibustion treatment groups were respectively subjected to moxibustion at 7-9 am and 5-7 pm. After 3 weeks of treatment, the tissues were collected at 6 time points during the next 24 hours. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to test the mRNA expression of CLOCK and BMAL1 in the hypothalamus and synovial tissues. CLOCK and BMAL1 protein expression in synovial tissues were detected with western blot. RESULTS: Compared to group A, group B showed significantly down-regulated expression levels of CLOCK and BMLA1 at synovial tissue (P < 0.05), while no statistically significant difference was found in the hypothalamus (P > 0.05). The expression levels of CLOCK and BMLA1 were up-regulated in the moxibustion treatment groups in different tissues, especially in synovial tissue (P < 0.05) compared to group B. Nevertheless, no difference was observed between groups C and D (P > 0.05). CONCLUSIONS: Moxibustion could treat RA by modulating clock core genes CLOCK and BMAL1 to regulate the circadian rhythm. However, there was no significant difference between the 7-9 am moxibustion treatment group and the 5-7 pm moxibustion treatment group. This study provides a basis for research on moxibustion in the treatment of RA.

Prunella vulgaris L. - A Review of its Ethnopharmacology, Phytochemistry, Quality Control and Pharmacological Effects.

Prunella vulgaris L. (PVL) is dried fruit spike of Lamiacea plant Prunella vulgaris L., which is a perennial herb with medicinal and edible homology used for thousands of years. PVL is bitter, acrid, cold, and belongs to the liver and gallbladder meridians. It clears the liver and dissipate fire, improve vision, disperse swelling, and has satisfactory clinical therapeutic effects on many diseases such as photophobia, dizziness, scrofula, goiter, breast cancer. The collection of information and data related to PVL comes from literatures retrieved and collated from various online scientific databases (such as CNKI, VIP, PubMed, Web of Science, Research Gate, Science Database), ancient books of traditional chinese medicine (Encyclopedia of Traditional Chinese Medicine, Classics of Traditional Chinese Medicine, Dictionary of Traditional Chinese Medicine), and Doctoral and Master's Dissertations. Currently, the major chemical constituents isolated and identified from PVL are triterpenoids, steroids, flavonoids, phenylpropanoids, organic acids, volatile oils and polysaccharides. Modern pharmacological studies have shown that PVL has a wide range of pharmacological activities, including anti-inflammatory, anti-tumor, antibacterial and antiviral effects, as well as immune regulation, antihypertensive, hypoglycemic, lipid-lowering, antioxidant, free radical scavenging, liver protection, sedative and hypnotic effects. This paper reviewes the botany, ethnopharmacology, traditional application, phytochemistry, analytical methods, quality control, pharmacological effects of PVL. It can be used not only as medicine, but also gradually integrated into the "medicine and food homology" and "Chinese medicine health" boom. More importantly, it has great potential for drug resources development. This paper deeply discusses the shortcomings of current PVL research, and proposes corresponding solutions, in order to find a breakthrough point for PVL research in the future. At the same time, it is necessary to further strengthen the research on its medicinal chemistry, mechanism of action and clinical application efficacy in the future, and strive to extract, purify and synthesize effective components with high efficiency and low toxicity, so as to improve the safety and rationality of clinical medication.

Effect of Levothyroxine Supplementation on the Cardiac Morphology and Function in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis.

CONTEXT: The impact of abnormal thyroid hormone levels on the cardiovascular system has been explored for decades. Recent emerging evidence suggests that subclinical thyroid dysfunction, especially subclinical hypothyroidism (SCH), significantly affects cardiac indices. OBJECTIVE: We aimed to determine whether levothyroxine (LT4), commonly used to treat hypothyroidism, affects cardiovascular indices in SCH patients. METHODS: This is a systematic review and meta-analysis. We searched online databases for studies analyzing cardiac morphology and functional changes in SCH patients before and after LT4 supplementation. A total of 294 SCH patients participated and finished the follow-up. The standard mean difference and 95% CI were calculated in fixed or random-effects models. The clinical outcomes analyzed in this study included 18 indicators, mainly covering cardiac morphology, myocardial performance (including various indicators of systolic and diastolic function), mitral wave flow, and systemic vascular resistance. RESULTS: A total of 11 studies met our search criteria. All studies explicitly mentioned that serum thyrotropin levels decreased to normal at follow-up. Our results suggest that the cardiac output (CO), left ventricular ejection fraction (LVEF), and the ratio of peak E velocity/peak A velocity were all significantly increased after LT4 supplementation compared with the baseline level. However, we found no clear evidence of significant morphological changes in the heart. CONCLUSION: Judging from the obvious changes in the CO, LVEF, and E/A ratio, LT4 supplementation can effectively improve the cardiac systolic and diastolic dysfunction prevalent in SCH patients. This study provides evidence of the recommendation for LT4 supplementation in adult SCH patients.

Effectiveness of acupuncture for patients with vascular dementia: A systematic review and meta-analysis.

OBJECTIVES: This meta-analysis assessed the treatment effectiveness of acupuncture in patients with vascular dementia. METHODS: The PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure were searched to identify eligible randomized controlled trials (RCTs). The odds ratios (ORs) and weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the pooled effect estimates using a random-effects model for categorical and continuous outcomes, respectively. RESULTS: Thirty-four RCTs (2672 patients) were selected for the final meta-analysis. The use of acupuncture showed association with an increased incidence of effective rate (OR: 3.28; 95 % CI: 2.54-4.24; P < 0.001). The pooled WMDs revealed that acupuncture was significantly associated with an improvement in the Hasegawa dementia scale (HDS) (WMD: 4.31; 95 % CI: 3.15-5.47; P < 0.001), and Mini-Mental State Examination scores (MMSE) (WMD: 3.07; 95 % CI: 2.40-3.74; P < 0.001). However, the use of acupuncture showed no association with the level of Activities of daily living (ADL) (WMD: 1.93; 95 % CI: - 2.53 to 6.38; P = 0.397). Finally, acupuncture was associated with lower levels of Scale for the differentiation of syndromes of vascular dementia (SDSVD) (WMD: - 2.15; 95 % CI: - 4.14 to - 0.16; P = 0.034), and National Institutes of Health stroke scale (NIHSS) (WMD: - 3.90; 95 % CI: - 4.87 to - 2.94; P < 0.001). CONCLUSIONS: Acupuncture is probably helpful in vascular stroke, but strong supportive data are not yet available. Acupuncture should be used cautiously, owing to the analysis of this study based on low to moderate evidence. Further high-quality, large-scale RCTs should be conducted.