Systematic evaluation and meta-analysis of Flunarizine Hydrochloride combined with traditional Chinese medicine decoction in the treatment of migraine headaches.

OBJECTIVES: To systematically evaluate the efficacy and superiority of Flunarizine Hydrochloride when combined with Traditional Chinese Medicine (TCM) Decoctions in treating migraine headaches. METHOD: The authors conducted a comprehensive search for clinical Randomized Controlled Trials (RCTs) investigating the combination of Flunarizine Hydrochloride with Chinese herbal decoctions in treating migraines. The databases searched included CNKI, VIP, Wanfang, PubMed, WOI, Cochrane Library, and Embase, covering the period from January 1, 2019, to November 10, 2023. Two independent researchers meticulously screened, extracted, and assessed the relevant data, employing the Revman 5.3 software for meta-analysis. RESULTS: The meta-analysis revealed that, in comparison to Flunarizine Hydrochloride used in isolation, the combination with Chinese herbal decoctions markedly enhanced the effective rate (RR = 1.26, 95 % CI [1.18, 1.34], p < 0.0001). Moreover, significant improvements were observed in the TCM symptom score (MD = 4.97, 95 % CI [-6.74, -3.19], p < 0.00001). The observation group demonstrated a statistically significant improvement in endothelin levels compared to the control group (I2 = 85 %, MD = -13.66, 95 % CI [-17.87, -9.45], p = 0.0001). The observation group showed a significant reduction in NRS scores compared to the control group, indicating better outcomes (I2 = 95 %, MD = -2.11, 95 % CI [-3.09, -1.12], p < 0.0001). The observation group was superior to the control group in terms of the reduction in the number of episodes (I2 = 63 %, MD = -1.16, 95 % CI [-1.45, -0.87], p = 0.007). CONCLUSIONS: The confluence of Flunarizine Hydrochloride with traditional Chinese medicine decoctions in treating migraine patients demonstrated substantial clinical efficacy and improvement in TCM symptom score over the use of Flunarizine Hydrochloride alone.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Dynamic ctDNA-based analysis of drug-resistant gene alterations at RAS/BRAF wild-type metastatic colorectal cancer patients after cetuximab plus chemotherapy as the first-line treatment.

BACKGROUND: The purpose of this study was to explore the dynamic changes of genomic mutations and their correlations with the efficacy in metastatic colorectal cancer (mCRC) patients treated with cetuximab plus mFOLFOX as the first-line treatment. METHODS: We included mCRC patients from January 2018 to October 2020 as a studied cohort which were treated with cetuximab plus mFOLFOX as first line therapy. Blood samples were collected for circulating tumor DNA (ctDNA) test at three timepoints: before the first-line therapy(baseline), at the time of first-line progression and at the time of second-line progression. Progression-free survival was considered as the primary endpoint while objective response rate and overall survival were determined as the secondary endpoints. RESULTS: Totally 39 patients received first-line treatment, of which 25 patients entered the second-line treatment, while 10 patients entered the third-line treatment. The median follow-up time was 16.4 months (95 %CI, 14.8-19.3). Along the treatment from first-line progress disease (PD) to second-line PD, proportions of TP53 (12/18, 67 %), APC (10/18, 56 %), FBXW7 (3/18, 17 %), and AMER1 (2/18, 11 %) were gradually increased according to results of single nucleotide variation (SNV). CONCLUSIONS: Resistant gene mutations caused by anti-EGFR drugs in RAS/BRAF wild-type mCRC patients can be observed by dynamic ctDNA analysis. TP53 and AMER1 mutations, tumor mutational burden (TMB) levels, and TP53/AMER1 co-mutation may predict the efficacy of the first-line cetuximab-contained treatment. Situations of genetic mutations were differentiated from first-line PD to second-line PD, which indicated that mutation detection may contribute to predict prognosis of mCRC patients.

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

Background: We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods: We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results: In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions: Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

Lupus nephritis or not? A simple and clinically friendly machine learning pipeline to help diagnosis of lupus nephritis.

OBJECTIVE: Diagnosis of lupus nephritis (LN) is a complex process, which usually requires renal biopsy. We aim to establish a machine learning pipeline to help diagnosis of LN. METHODS: A cohort of 681 systemic lupus erythematosus (SLE) patients without LN and 786 SLE patients with LN was established, and a total of 95 clinical, laboratory data and 17 meteorological indicators were collected. After tenfold cross-validation, the patients were divided into training set and test set. The features selected by collective feature selection method of mutual information (MI) and multisurf were used to construct the models of logistic regression, decision tree, random forest, naive Bayes, support vector machine (SVM), light gradient boosting (LGB), extreme gradient boosting (XGB), and artificial neural network (ANN), the models were compared and verified in post-analysis. RESULTS: Collective feature selection method screens out antistreptolysin (ASO), retinol binding protein (RBP), lupus anticoagulant 1 (LA1), LA2, proteinuria and other features, and the hyperparameter optimized XGB (ROC: AUC = 0.995; PRC: AUC = 1.000, APS = 1.000; balance accuracy: 0.990) has the best performance, followed by LGB (ROC: AUC = 0.992; PRC: AUC = 0.997, APS = 0.977; balance accuracy: 0.957). The worst performance is naive Bayes model (ROC: AUC = 0.799; PRC: AUC = 0.822, APS = 0.823; balance accuracy: 0.693). In the composite feature importance bar plots, ASO, RF, Up/Ucr, and other features play important roles in LN. CONCLUSION: We developed and validated a new and simple machine learning pathway for diagnosis of LN, especially the XGB model based on ASO, LA1, LA2, proteinuria, and other features screened out by collective feature selection.

Efficacy and safety of tacrolimus-based treatment for non-rapidly progressive IgA nephropathy.

In this study, we aimed to evaluate the efficacy and safety of tacrolimus-based treatment for immunoglobulin A nephropathy (IgAN). We retrospectively reviewed 127 adult patients with primary IgAN with 24 h urine total protein quantity (24 h UTP) ≥ 1 g and serum creatinine ≤3 mg/dL. All patients were divided into tacrolimus (TAC) and control (non-TAC) groups according to the treatment strategy. Proteinuria remission, remission rate, and adverse events were compared between the two groups. Among the 127 patients, 61 received TAC-based treatment and 66 received non-TAC treatment. TAC group exhibited a more rapid decline in proteinuria than the non-TAC group at 3, 9, and 12 months (p = 0.049, 0.001, and 0.018, respectively). Remission rates at 1, 3, 6, 9, and 12 months were 41.0, 68.9, 80.3, 90.2, and 88.5%, respectively, in the TAC group. These rates were higher than those in the control group at 3, 9, and 12 months (p = 0.030, 0.008, and 0.026, respectively). Complete remission rates at 1, 3, 6, 9, and 12 months were 6.56, 19.7, 37.7, 54.1, and 62.3%, respectively, in the TAC group. These rates were higher than those in the control group at 9 and 12 months (p = 0.013 and 0.008, respectively). The estimated mean time to complete remission was significantly shorter in the TAC group than in the control group (p = 0.028). TAC did not increase the incidence of adverse events. In conclusion, TAC accelerated proteinuria remission in patients with non-rapidly progressive IgAN with no increased risk of adverse events. Further prospective randomized controlled trials are necessary to validate our findings.

Optimization of extraction conditions for LC-ToF-MS analysis of mevalonate pathway metabolites in engineered E. coli strain via statistical experimental designs.

Isoprenoids give rise to many functional products used today such as flavours, fragrances and even pharmaceutical compounds. Mevalonate pathway metabolites are the key intermediates that affect the production yield of isoprenoids. With increasing demand and benefit of isoprenoids, the present study adopts Analytical Quality-by-Design (AQbD) approach to establish an efficacious extraction protocol prior to the determination of mevalonate pathway metabolites in an engineered Escherichia coli model. The statistical experimental design approach, described in this work, has successfully validated an optimised sample preparation method i.e., using acetonitrile: 50 mM ammonium formate (pH 9.5) (7:3) (ACN73) at -20 °C for 10 min without solvent evaporation to retain the targeted mevalonate metabolites in engineered E. coli strain. The study also demonstrates the use of liquid chromatography paired with a Time-of-Flight Mass Spectrometer (LC-ToF-MS) for the quantitative analysis of the mevalonate pathway metabolites in E. coli. The analytical method was validated in accordance with guidelines in Metabolomics Standards Initiative and ICH Q2 (R1) with analyte spike recoveries at 80% and above. In short, the present study overcomes the one-variable-at-a-time (OVAT) limitations in analytical development, minimises metabolite losses and gives better cost and time efficiencies by eliminating the solvent evaporation and swapping process. This work highlights the importance of analytical methods development in microbial metabolomics studies.

Ratiometric fluorescent sensing of phosphate ion in environmental water samples using flavin mononucleotide-functionalized Fe3O4 particles.

Phosphate ion (PO43-) serves as an important nutrient carrier to support the growth of aquatic animals and plants in aquatic systems. However, excess concentrations of PO43- are the key factor responsible for eutrophication, resulting in rapid deterioration of water quality. Therefore, accurate determination of PO43- is of great significance in water quality and security. In this study, flavin mononucleotide (FMN), an intracellular form of vitamin B2, was used as fluorophore. A novel "off-on" fluorescent sensing platform (FMN@Fe3O4) was fabricated for selective and sensitive detection of PO43-, and showed excellent fluorescence response and good selectivity for PO43- detection. With the addition of PO43-, the fluorescence intensity restored is proportional to PO43- concentration in the quantification range of 50 nM-0.75 µM with a limit of detection as low as 20 nM (0.62 µg.L-1, calculated by P element). An adsorption/desorption sensing mechanism via an in-depth analysis of the interfacial interaction between PO43- and FMN@Fe3O4 is proposed. FMN is first adsorbed by its terminal phosphate group on Fe3O4 particles to quench fluorescence. Free PO43- replaces the adsorbed FMN and restores the quenched fluorescence to achieve the aim of PO43- detection. In addition, this sensing system has been successfully validated in real water sample analysis and all reagents involved are nontoxic, environmentally benign, and easily-available. Therefore, this assay has great applicability in water quality monitoring.

Clinacanthus nutans aqueous leaves extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of ß-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach. AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE. MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot. RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model. CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

Metabolomics and modelling approaches for systems metabolic engineering.

Metabolic engineering involves the manipulation of microbes to produce desirable compounds through genetic engineering or synthetic biology approaches. Metabolomics involves the quantitation of intracellular and extracellular metabolites, where mass spectrometry and nuclear magnetic resonance based analytical instrumentation are often used. Here, the experimental designs, sample preparations, metabolite quenching and extraction are essential to the quantitative metabolomics workflow. The resultant metabolomics data can then be used with computational modelling approaches, such as kinetic and constraint-based modelling, to better understand underlying mechanisms and bottlenecks in the synthesis of desired compounds, thereby accelerating research through systems metabolic engineering. Constraint-based models, such as genome scale models, have been used successfully to enhance the yield of desired compounds from engineered microbes, however, unlike kinetic or dynamic models, constraint-based models do not incorporate regulatory effects. Nevertheless, the lack of time-series metabolomic data generation has hindered the usefulness of dynamic models till today. In this review, we show that improvements in automation, dynamic real-time analysis and high throughput workflows can drive the generation of more quality data for dynamic models through time-series metabolomics data generation. Spatial metabolomics also has the potential to be used as a complementary approach to conventional metabolomics, as it provides information on the localization of metabolites. However, more effort must be undertaken to identify metabolites from spatial metabolomics data derived through imaging mass spectrometry, where machine learning approaches could prove useful. On the other hand, single-cell metabolomics has also seen rapid growth, where understanding cell-cell heterogeneity can provide more insights into efficient metabolic engineering of microbes. Moving forward, with potential improvements in automation, dynamic real-time analysis, high throughput workflows, and spatial metabolomics, more data can be produced and studied using machine learning algorithms, in conjunction with dynamic models, to generate qualitative and quantitative predictions to advance metabolic engineering efforts.

High expression of long noncoding RNA plasmacytoma variant translocation 1 is an independent risk factor for recurrence after radiofrequency ablation in atrial fibrillation patients.

Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-ß1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-ß1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence.

Periodontitis Is Associated With Heart Failure: A Population-Based Study (NHANES III).

Objectives: The aim of this study was to investigate the relationship between periodontitis and heart failure using the Third National Health and Nutrition Examination Survey (NHANES III). Methods: Participants who had received a periodontal examination were included and investigated for the occurrence of heart failure. The included participants were divided into no/mild periodontitis and moderate/severe periodontitis groups according to their periodontal status. Weighted prevalence of heart failure was calculated, and weighted logistic regressions models were used to explore the association between periodontitis and heart failure. Possible influencing factors were then explored through subgroup analysis. Results: Compared with that of the no/mild periodontitis group, the incidence of heart failure in participants with moderate/severe periodontitis was 5.72 times higher (95% CI: 3.76-8.72, p < 0.001). After adjusting for gender, age, race, body mass index, poverty income ratio, education, marital status, smoking status, drinking status, hypertension, diabetes, stroke, and asthma, the results showed that the incidence of heart failure in the moderate/severe group was 3.03 times higher (95% CI: 1.29-7.13, p = 0.012). Subgroup analysis showed that criteria, namely, male, 40-60 years old, non-Hispanic white, body mass index >30, poverty income ratio ≥1, not more than 12 years of education, currently drinking, stroke but no diabetes, or asthma supported moderate/severe periodontitis as a risk factor for heart failure (p < 0.05). Conclusion: According to data from this nationally representative sample from the United States, periodontitis is associated with an increased risk of heart failure.

Population pharmacokinetics and IVIVC for mesalazine enteric-coated tablets.

Although in-vivo bioequivalence (BE) study serves as a golden standard for establishing interchangeability of oral dosage forms, it remains challenging for products with high inter-subject variability such as mesalazine enteric-coated tablet to fulfil the BE criteria set by regulatory authorities. Mesalazine, as a BCS class IV drug, targets to be delivered to distal ileum or colon with a pH-sensitive polymer coating for the remission of ulcerative colitis. Through population pharmacokinetic (PK) analysis and in-vitro in-vivo correlation (IVIVC) modeling on the dissolution and BE data of a generic enteric-coated product (EM) and its reference Salofalk® 250 mg tablet (SM), we for the first time revealed the underlying mechanism of the high inter-subject variability for such delayed-release formulation. It was also noted that the in-vivo start time of absorption (Ts) for EM and SM was positively correlated with their in-vitro lag time (Tlag) under the USP three-stage dissolution condition and reversely correlated with their in-vivo bioavailability. The varied oral bioavailability of mesalazine enteric-coated tablet was mainly due to the varied N-acetyltransferase activities along GI tract. Although such extensive intestinal first-pass metabolism with large individual differences led to a significant variation of mesalazine Cmax (coefficient of variation: 60-63.5%) and AUC0-t (coefficient of variation: 37.5-46.9%), the corresponding variations in the total absorbed mesalazine (mesalazine and its metabolite N-acetyl mesalazine) were significantly reduced by 12 to 45%. Since the BE purpose for mesalazine enteric-coated tablet focused on their comparable safety profiles, total absorbed mesalazine was recommended to be adopted for the development of the IVIVC model and BE evaluation for EM. All in all, our model-based approach has not only successfully identified the key factors that affect the BE of EM to guide its further formulation optimization, but also demonstrated the indispensable role of modeling in the development of generic pharmaceutical product at its early stages.

6-Gingerol, a functional polyphenol of ginger, reduces pulmonary fibrosis by activating Sirtuin1.

Pulmonary fibrosis in general is the final common outcome of various interstitial lung diseases. In recent years, the incidence of pulmonary fibrosis has been rising with poor prognosis. 6-gingerol is deemed as a functional polyphenol of ginger. The aim of the present study was to investigate the effect of 6-gingerol, on pulmonary fibrosis. Mice were randomly divided into four groups: control, bleomycin, bleomycin + 6-gingerol 100 mg/kg, bleomycin + 6-gingerol 250 mg/kg, and the survival rates of the groups were recorded. Pathological and fibrotic changes in the lungs were identified by H&E and Masson staining, respectively. The levels of hydroxyproline and protein deposited in lung tissues were then, respectively, determined by colorimetry and western blotting. Subsequently, the proportion of cells and inflammatory factors in the alveolar lavage fluid were estimated. Following the identification of the possibility of Sirtuin1 (SIRT1) in the pharmacological mechanism through molecular docking and western blotting, human embryonic lung fibroblasts MRC-5 were treated with TGF-ß1 and SIRT1 inhibitor to study the role of SIRT1 in the regulatory effect of 6-gingerol. From the results, 6-gingerol was found to increase the survival rate of mice and reduce lung pathology and fibrosis in mice. And, it significantly reduced the levels of hydroxyproline and the proteins deposited in lung tissues. Moreover, the number of neutrophils, basophils, monocytes, and the levels of inflammatory factors in the alveolar lavage fluid were also reduced. SIRT1 inhibitor blocked the function of 6-gingerol to inhibit fibrosis. To sum up, 6-gingerol relieves pulmonary fibrosis via activating SIRT1. This finding expands the pharmacological effect of 6-gingerol, and it is expected to advance the development of treatments for pulmonary fibrosis.

The spatial and temporal trends of severe periodontitis burden in Asia, 1990-2019: A population-based epidemiological study.

BACKGROUND: To investigate the long-term and spatial patterns of incidence, prevalence, and disability-adjusted life year (DALY) rates of severe periodontitis in Asia from 1990 to 2019, and to estimate the associations between disease burden and socioeconomic development using the Socio-Demographic Index (SDI). METHODS: Data were obtained from the global burden of disease study 2019. The average annual percent change (AAPC) was calculated to reflect temporal trends, spatial autocorrelation analysis was conducted to estimate the spatial characteristics, and spatial panel models were used to investigate the association between SDI and severe periodontitis burden. RESULTS: For Asia as a whole, the crude rates increased by 1.10% per year for incidence, 1.42% per year for prevalence, and 1.41% per year for DALY from 1990 to 2019. The age-standardized incidence, prevalence and DALY rates increased by 0.18%, 0.22%, and 0.23% per year, respectively. Spatially, the hot spots of age-standardized incidence, prevalence and DALY rates were located in Southern Asia, besides, these rates all showed increasing trends in most countries, and the increases were clustered in Southeastern Asia. Further, SDI showed a negative association with incidence (coef = -14.44; 95% CI: -24.63, -4.25) and prevalence (coef = -40.09; -51.81, -28.36), and a positive association with DALY rates (coef = 0.31; 0.23; 0.38). CONCLUSIONS: Severe periodontitis poses a serious public health challenge in Asian countries with increasing temporal trends and substantial spatial inequalities. Effective geographically targeted public health interventions and strategies are needed to address the growing burden associated with severe periodontitis.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers.

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage.

BACKGROUND: This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). METHODS: Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. RESULTS: Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. CONCLUSION: LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.

Progression of Symptoms Caused by Botryosphaeria dothidea on Apple Branches.

Until recently, the causal agent of Botryosphaeria canker was assumed to differ from that causing ring rot on fruit and warts on branches on apple trees in China and East Asia. However, recent research documented that Botryosphaeria dothidea caused both disease symptoms on apple. Inoculations with strains isolated from cankers and warts on branches were conducted to investigate symptom progression caused by B. dothidea and conditions inducing the two symptom types. The results confirmed that both cankers and warts are caused by B. dothidea. Warts are the results of hyperplasia and suberization of bark tissues induced by fungal infection, whereas cankers result from the rapid growth of hyphae from inside warts, lenticels, or wounds. Resistance to B. dothidea exists in living apple branches. When a living branch is infected via lenticels, the pathogen induces proliferation and suberization of cortical cells that restricts the growth and expansion of the hyphae, leading to warts. However, under certain stress conditions such as drought, the hyphae inside host tissues expand rapidly and kill cortical cells, leading to canker development. Host resistance may recover during active growth periods, which suppresses or even stops rapid expansion of the hyphae, leading to the intermediate symptom of canker warts. Abiotic factors, such as drought or high temperature in early spring, can result in rapid extension of colonized hyphae in branches and conversion of warts to cankers. Preventing this transition can be an important measure in managing Botryosphaeria canker on apple.

Trim47 is a critical regulator of cerebral ischemia-reperfusion injury through regulating apoptosis and inflammation.

Cerebral ischemia is a leading cause of death and long-term disability in the world. Tripartite motif-47 (Trim47), a member of the TRIM family proteins, has been reported to be involved in apoptosis and inflammation in various types of diseases. Nevertheless, the underlying molecular mechanism of Trim47 in cerebral ischemia/reperfusion (I/R) injury remains unclear. This study aimed to explore the role of Trim47 in cerebral I/R injury and the potential underlying mechanisms. The results indicated that Trim47 expression was markedly induced in rats after stroke onset. By the use of genetic approaches, we indicated that Trim47 knockdown significantly reduced the infarct size, mitigated the neurological deficits scores and decreased brain water contents in rats with cerebral I/R injury induced by middle cerebral artery occlusion (MCAO). In addition, Trim47 knockdown-alleviated cerebral I/R was correlated with the suppression of apoptosis through inhibiting Caspase-3 cleavage. Furthermore, reducing Trim47 apparently decreased the release of pro-inflammatory factors, including interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), in brain samples of MCAO rats, which was partly by the blockage of nuclear factor-kappa B (NF-κB) signaling. However, Trim47 over-expression markedly accelerated cerebral ischemia injury through promoting apoptosis and inflammation. The suppressive effects of Trim47 knockdown on cerebral I/R were verified in human neuron-like cells stimulated by oxygen and glucose deprivation (OGD). Thus, this study demonstrated a new mechanism for the effect of Trim47 on cerebral I/R injury, and targeting Trim47 might provide feasible therapies for stroke treatment.

[Effects and mechanism of salidroside on streptozotocin-induced mode rats of diabetic nephropathy].

OBJECTIVE: To investigate the effects and mechanism of salidroside(SAL) on model rats of diabetic nephropathy(DN). METHODS: Rats were divided into control, model, SAL(50 mg/kg), SAL(100 mg/kg) and SAL(200 mg/kg) groups. The rats beside in control group were injected with streptozotocin(STZ) combined with right nephrectomy. And rats in SAL(50, 100, 200 mg/kg) groups were received gavage with SAL(50, 100, 200 mg/kg). After 12 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for renal injury, the concentrations of urine protein, urine creatine(Ucr), blood urea nitrogen(BUN), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were measured by kits. Western blot was used to measure the protein levels of Collagen Ⅳ, fibronectin, E-cadherin, α-smooth muscle actin(α-SMA), N-cadherin, Smad2、Smad3, phosphorylated-Smad2(p-Smad2), p-Smad3 and transforming growth factor-ß1(TGF-ß1). RESULTS: Compared with control group, the renal injury of rats in model group was aggravated, the concentrations of urine protein, Ucr and BUN were elevated significantly, the apoptosis cells and positive cells of caspase-3 were increased; compared with model group, the renal injury of rats in SAL(100, 200 mg/kg) groups were alleviated markedly, the concentrations of urine protein, Ucr and BUN were reduced, the apoptosis cells and positive cells of caspase-3 were decreased notably. SAL(50 mg/kg) increased the concentration of SOD in DN model rats, SAL(100, 200 mg/kg) increased the concentrations of SOD and GSH-Px, decreased the level of MDA. Meanwhile, the inhibition of collagen Ⅳ, fibronrctin, α-SMA, and N-cadherin and the induction of E-cadherin in DN rats were induced by SAL(100, 200 mg/kg). In addition, SAL(100, 200 mg/kg) reduced the ratio of p-Smad2/Smad2, p-Smad3/Smad3 and the level of TGF-ß1(P<0.05 or P<0.01). CONCLUSION: SAL can inhibit renal fibrosis of STZ-induced DN model rats, and the mechanism may be related to inhibition of TGF-ß1/Smad pathway.