Effect of dietary Glycyrrhiza polysaccharides on growth performance, hepatic antioxidant capacity and anti-inflammatory capacity of broiler chickens.

The primary aim of this study was to investigate the impact of varying levels of dietary Glycyrrhiza polysaccharides (GPS) on the health status of broiler chickens. A total of 288 1-day-old Arbor Acres broilers were randomly assigned to four groups with six replicates, consisting of 12 chickens in each replicate. The control group (CON) was provided with the basal diet, while the experimental groups were administered 300, 600, and 900 mg/kg of GPS in the basal diet for 42 days. The results demonstrated a significant enhancement in average daily gain (ADG) as a result of GPS supplementation (P < 0.05). The dietary GPS significantly elevated total antioxidation capability (T-AOC) and the activity of antioxidant enzymes (P < 0.05), while effectively reducing the levels of malondialdehyde (MDA) in the serum and liver (P < 0.05). Administration of GPS notably inhibited the toll-like receptor 4 (TLR4) signaling pathway (P < 0.05), decreased interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) levels (P < 0.05), and increased IL-4 and IL-10 levels (P < 0.05). Additionally, the expression of crucial regulators involved in liver lipid metabolism, including sterol regulatory element binding protein 1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were significantly reduced (P < 0.05). In contrast, the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) was significantly enhanced in the GPS-supplemented groups (P < 0.05). In conclusion, the supplementation of GPS positively influenced the growth performance, the anti-inflammatory and antioxidant capacity of the liver, as well as liver lipid metabolism in broilers.

Pectin based hydrogel with covalent coupled doxorubicin and limonin loading for lung tumor therapy.

Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM195-co-AH54) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition, the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.

Chromatin architecture of two different strains of Artemisia annua reveals the alterations in interaction and gene expression.

MAIN CONCLUSION: The hierarchical architecture of chromatins affects the gene expression level of glandular secreting trichomes and the artemisinin biosynthetic pathway-related genes, consequently bringing on huge differences in the content of artemisinin and its derivatives of A. annua. The plant of traditional Chinese medicine "Qinghao" is called Artemisia annua L. in Chinese Pharmacopoeia. High content and the total amount of artemisinin is the main goal of A. annua breeding, nevertheless, the change of chromatin organization during the artemisinin synthesis process has not been discovered yet. This study intended to find the roles of chromatin structure in the production of artemisinin through bioinformatics and experimental validation. Chromosome conformation capture analysis was used to scrutinize the interactions among chromosomes and categorize various scales of chromatin during artemisinin synthesis in A. annua. To confirm the effect of the changes in chromatin structure, Hi-C and RNA-sequencing were performed on two different strains to find the correlation between chromatin structure and gene expression levels on artemisinin synthesis progress and regulation. Our results revealed that the frequency of intra-chromosomal interactions was higher in the inter-chromosomal interactions between the root and leaves on a high artemisinin production strain (HAP) compared to a low artemisinin production strain (LAP). We found that compartmental transition was connected with interactions among different chromatins. Interestingly, glandular secreting trichomes (GSTs) and the artemisinin biosynthetic pathway (ABP) related genes were enriched in the areas which have the compartmental transition, reflecting the regulation of artemisinin synthesis. Topologically associated domain boundaries were associated with various distributions of genes and expression levels. Genes associated with ABP and GST in the adjacent loop were highly expressed, suggesting that epigenetic regulation plays an important role during artemisinin synthesis and glandular secreting trichomes production process. Chromatin structure could show an important status in the mechanisms of artemisinin synthesis process in A. annua.

A novel biomass pyrogenic index and its application coupled with black carbon for improving polycyclic aromatic hydrocarbon source identification.

To accurately subdivide the sources of polycyclic aromatic hydrocarbons (PAHs), the composition characteristics of 36 total polycyclic hydrocarbons (T-PAHs; 16 parent PAHs and 20 alkylated PAHs [A-PAHs]) in biomass-residue samples were analyzed. A novel biomass pyrogenic index (BPI) was defined based on A-PAH-fingerprinting differences between biomass-combustion and petroleum sources of PAHs and the sum of the concentrations of pyrene, fluoranthene, benzo[a]anthracene, and alkylated homologs) divided by the ∑value of EPA PAHs with 2-3 rings. BPIs of < 0.5 and > 0.5 indicated that the PAHs originated mainly from biomass combustion and petroleum, respectively. And the ∑targeted A-PAH pairs influencing the BPI/black carbon (BC) ratio was used to identify PAH sources in surface-sediment samples, using 0.5 as the threshold to distinguish between different sources across the strait. The columnar sediments were used to verify the accuracy of two source-identification methods. The results revealed that the main PAH sources changed since 2005, which is highly consistent with those obtained using positive matrix factors and a changing trend in the main types of local energy use. These results highlight the significance of A-PAHs in accurately identifying PAH sources and suggest that applying compositional differences in BC from different sources for PAH-source identification merits further study.

Biodegradable hydrogel from pectin and carboxymethyl cellulose with Silibinin loading for lung tumor therapy.

Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo, and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.

Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer.

Cancer is one of the most serious malignant diseases, and chemotherapy is cancer's main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlic's active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentration-dependently inhibited TMEM16A currents with an IC50 of 24.35 ± 4.14 µM. Allicin thiosulfinate moieties bound with R535A/E624A/E633A residues of TMEM16A blocked the ion transport function and downregulated TMEM16A protein expression affecting the mitogen-activated protein kinase signal transduction. Then, allicin reduced the viability and migration of LA795 cells, and induced cell apoptosis. Moreover, multitarget combination administration results indicated that the therapeutic effect of 3.56 mg/kg allicin and 3 mg/kg cisplatin combined administration was superior to the superposition of the two drugs alone, demonstrating that the anticancer effects of allicin and cisplatin were synergistic. In addition, low-concentration combined administration also avoided the side effects of cisplatin in mice. Based on the good tumor suppressor effect and high biosafety of allicin and cisplatin combination in vivo, allicin can be used for food adjuvant therapy of cisplatin chemotherapy.

Self-healing pectin/cellulose hydrogel loaded with limonin as TMEM16A inhibitor for lung adenocarcinoma treatment.

Lung cancer as one of the highest incident malignant tumors did not receive satisfactory chemotherapy due to lack of specific drug targets and targeted drugs. This study screened a new effective lung tumor inhibitor limonin from herbal medicine, which inhibited proliferation and promoted apoptosis of lung adenocarcinoma cells by targeting specific high expressed TMEM16A ion channel. Moreover, a novel biodegradable self-healing hydrogel was prepared from acylhydrazide functionalized carboxymethyl cellulose (CMC-AH) and oxidized pectin (pec-CHO) to reduce the side effects of the limonin to the body. The hydrogels showed fast gelation, good biocompatibility and sustained limonin release property. The limonin-loaded hydrogel significantly inhibited the growth of lung adenocarcinoma in xenografts mice because the limonin inhibited the proliferation, migration and promoted apoptosis of LA795 cells, and eliminated the acute toxicity through sustained release from the hydrogel. Combined the antitumor performance of the limonin and sustained release of pec-CHO/CMC-AH hydrogel, this limonin/hydrogel system achieved satisfactory antitumor effect and eliminated side effects in vivo. Therefore, this system has great potential application for enhanced lung adenocarcinoma therapy.

Imaging Diagnosis of Primary Liver Cancer Using Magnetic Resonance Dilated Weighted Imaging and the Treatment Effect of Sorafenib.

Objective: This work explores the application value of dilated weighted imaging (DWI) in the diagnosis of primary liver cancer (PLC) and the effect of sorafenib in the treatment of PLC. Methods: 88 patients with PLC who were treated in The First Affiliated Hospital of Northwest University from March 2019 to March 2021 were selected and randomly rolled into an experimental group and a control group, with 44 cases in each group. Patients in both groups were treated with transcatheter arterial chemoembolization (TACE), and the patients in the experimental group were treated with oral sorafenib on the basis of TACE. The indicators of complications, short-term efficacy (STE), and long-term efficacy (LTE) of the two groups were observed. All patients received DWI and magnetic resonance (MR) plain scan. The diagnostic accuracy and misdiagnosis rate of the two methods in diagnosing the PLC were compared. Results: The accuracy, specificity, and sensitivity of MR plain scan were 68%, 88%, and 89%, respectively, while those of DWI were 96%, 95%, and 94.2%, respectively. It indicated that the accuracy, specificity, and sensitivity of DWI in diagnosing lesions were better than those of MR plain scan, especially the diagnostic accuracy (P < 0.05). The objective response rate (ORR) and disease control rate (DCR) of the STE in the experimental group were 30% and 97%, respectively, and those in the control group were 6% and 54.5%, respectively. The experimental group's mean progression-free survival (mPFS) and mean overall survival (mOS) were 12 and 25 months, respectively, while the control group's were 8 and 19 months, respectively. It was concluded that the mPFS and mOS of patients receiving TACE combined with oral sorafenib were much higher than those receiving TACE only (P < 0.05). Conclusion: DWI and TACE combined with sorafenib had high application value in the diagnosis and treatment of PLC.

Caffeic Acid, an Active Ingredient in Coffee, Combines with DOX for Multitarget Combination Therapy of Lung Cancer.

Adjuvant diet therapy is an important means of comprehensive treatment of cancer. It is recognized by patients for its high safety, painlessness, and ease to operate. However, the development of adjuvant dietary therapy is limited by unclear targets and unclear anticancer mechanisms. In this work, caffeic acid was found as an inhibitor of TMEM16A with an IC50 of 29.47 ± 3.19 µM by fluorescence quenching and whole-cell patch-clamp experiments. Caffeic acid regulated the proliferation, migration, and apoptosis of lung cancer cells targeting TMEM16A, which was detected by CCK-8, colony formation, wound healing, and Annexin V assays. In addition, molecular docking combined with site-directed mutagenesis confirmed that the binding sites of caffeic acid to TMEM16A were D439, E448, and R753. Western blot results indicated that caffeic acid regulated the growth of lung cancer through the MAPK pathway. In vitro experiments showed that the inhibitory effect of caffeic acid combined with hydroxydaunorubicin (DOX) on lung cancer cell growth was better than a double concentration of any single dose. In vivo pharmacokinetic experiments and tumor xenograft experiments indicated that the combination of 5.4 mg/kg caffeic acid and 4.1 mg/kg DOX achieved 85.6% tumor suppression rate and offset the side effects. Therefore, caffeic acid is a safe and efficient antitumor active ingredient of food that can enhance the antitumor effect of DOX.

A Comparative Analysis of the Chloroplast Genomes of Four Polygonum Medicinal Plants.

Polygonum is a generalized genus of the Polygonaceae family that includes various herbaceous plants. In order to provide aid in understanding the evolutionary and phylogenetic relationship in Polygonum at the chloroplast (cp) genome-scale level, we sequenced and annotated the complete chloroplast genomes of four Polygonum species using next-generation sequencing technology and CpGAVAS. Then, repeat sequences, IR contractions, and expansion and transformation sites of chloroplast genomes of four Polygonum species were studied, and a phylogenetic tree was built using the chloroplast genomes of Polygonum. The results indicated that the chloroplast genome construction of Polygonum also displayed characteristic four types of results, comparable to the published chloroplast genome of recorded angiosperms. The chloroplast genomes of the four Polygonum plants are highly consistent in genome size (159,015 bp-163,461 bp), number of genes (112 genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes), gene types, gene order, codon usage, and repeat sequence distribution, which identifies the high preservation among the Polygonum chloroplast genomes. The Polygonum phylogenetic tree was recreated by a full sequence of the chloroplast genome, which illustrates that the P. bistorta, P. orientale, and P. perfoliatum are divided into the same branch, and P. aviculare belongs to Fallopia. The precise system site of lots base parts requires further verification, but the study would provide a basis for developing the available genetic resources and evolutionary relationships of Polygonum.

Bifidobacterium lactis Probio-M8 Adjuvant Treatment Confers Added Benefits to Patients with Coronary Artery Disease via Target Modulation of the Gut-Heart/-Brain Axes.

Accumulating evidence suggests that gut dysbiosis may play a role in cardiovascular problems like coronary artery disease (CAD). Thus, target steering the gut microbiota/metabolome via probiotic administration could be a promising way to protect against CAD. A 6-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the added benefits and mechanism of the probiotic strain, Bifidobacterium lactis Probio-M8, in alleviating CAD when given together with a conventional regimen. Sixty patients with CAD were randomly divided into a probiotic group (n = 36; received Probio-M8, atorvastatin, and metoprolol) and placebo group (n = 24; placebo, atorvastatin, and metoprolol). Conventional treatment significantly improved the Seattle Angina Questionnaire (SAQ) scores of the placebo group after the intervention. However, the probiotic group achieved even better SAQ scores at day 180 compared with the placebo group (P < 0.0001). Moreover, Probio-M8 treatment was more conducive to alleviating depression and anxiety in patients (P < 0.0001 versus the placebo group, day 180), with significantly lower serum levels of interleukin-6 and low-density lipoprotein cholesterol (P < 0.005 and P < 0.001, respectively). In-depth metagenomic analysis showed that, at day 180, significantly more species-level genome bins (SGBs) of Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, and Butyricicoccus porcorum were detected in the probiotic group compared with the placebo group, while the abundances of SGBs representing Flavonifractor plautii and Parabacteroides johnsonii decreased significantly among the Probio-M8 receivers (P < 0.05). Furthermore, significantly more microbial bioactive metabolites (e.g., methylxanthine and malonate) but less trimethylamine-N-oxide and proatherogenic amino acids were detected in the probiotic group than placebo group during/after intervention (P < 0.05). Collectively, we showed that coadministering Probio-M8 synergized with a conventional regimen to improve the clinical efficacy in CAD management. The mechanism of the added benefits was likely achieved via probiotic-driven modulation of the host's gut microbiota and metabolome, consequently improving the microbial metabolic potential and serum metabolite profile. This study highlighted the significance of regulating the gut-heart/-brain axes in CAD treatment. IMPORTANCE Despite recent advances in therapeutic strategies and drug treatments (e.g., statins) for coronary artery disease (CAD), CAD-related mortality and morbidity remain high. Active bidirectional interactions between the gut microbiota and the heart implicate that probiotic application could be a novel therapeutic strategy for CAD. This study hypothesized that coadministration of atorvastatin and probiotics could synergistically protect against CAD. Our results demonstrated that coadministering Probio-M8 with a conventional regimen offered added benefits to patients with CAD compared with conventional treatment alone. Our findings have provided a wide and integrative view of the pathogenesis and novel management options for CAD and CAD-related diseases.

Endophytic bacterial and fungal community compositions in different organs of ginseng (Panax ginseng).

Panax ginseng (Panax ginseng C. A. Mey.) is a perennial herb of the genus ginseng, which is used as medicine with dried roots and rhizomes. With the deepening of research on ginseng, the chemical components and pharmacological effects of ginseng have gradually been discovered. Endophytes are beneficial to host plants. However, the composition of endophytes in different organs from ginseng is poorly elucidated. The report of ginsenoside production by endophytic microbes isolated from Panax sp., motivated us to explore the endophytic microbial diversity related to the roots, stems, and leaves. In this study, the V5-V7 variable region of endophytic bacteria 16S rRNA gene and V1 variable region of endophytic fungi ITS gene in different organs were analyzed by high-throughput sequencing. The diversity and abundance of endophytic microbes in the three organs are different and are affected by the organs. For example, the most abundant endophytic bacterial genus in roots was Mycobacterium, while, the stems and leaves were Ochrobactrum. Similarly, the fungal endophytes, Coniothyrium and Cladosporium, were also found in high abundance in stems, in comparison to roots and leaves. The Shannon index shows that the diversity of endophytic bacteria in roots is the highest, and the richness of endophytic bacterial was root > stem (p < 0.05). Principal coordinate analysis showed that there were obvious microbial differences among the three groups, and the endophytic bacterial composition of the leaves was closer to that of the roots. This study provides an important reference for the study of endophytic microorganisms in ginseng.

Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats.

Diabetic nephropathy (DN), a severe microvascular complication of diabetes, is one of the leading causes of end-stage renal disease. Huayu Tongluo Recipe (HTR) has been widely used in the clinical treatment of DN in China, and its efficacy is reliable. This study aimed to explore the renoprotective effect of HTR and the underlying mechanism. Male Sprague-Dawley rats were fed with high sugar and fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. Rats in each group were respectively given drinking water, HTR, and irbesartan by gavage for 16 weeks. 24-hour urine samples were collected every 4 weeks to detect the content of total protein and 8-OHdG. Blood samples were taken to detect biochemical indicators and inflammatory markers at the end of 16th week. Renal tissue was collected to investigate pathological changes and to detect oxidative stress and inflammatory markers. AMPK/Nrf2 signaling pathway and fibrosis-related proteins were detected by immunohistochemistry, immunofluorescence, real-time PCR, and western blot. 24h urine total protein (24h UTP), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), and triglyceride (TG) were decreased in the rats treated with HTR, while there was no noticeable change of blood glucose. HTR administration decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in kidneys, complying with reduced 8-OHdG in the urine. The levels of TNF-α, IL-1ß, and MCP1 and the expression of nuclear NFκB were also lower after HTR treatment. Furthermore, HTR alleviated pathological renal injury and reduced the accumulation of extracellular matrix (ECM). Besides, HTR enhanced the AMPK/Nrf2 signaling and increased the expression of HO-1 while it inhibited the Nox4/TGF-ß1 signaling in the kidneys of STZ-induced diabetic rats. HTR can inhibit renal oxidative stress and inflammation to reduce ECM accumulation and protect the kidney through activating the AMPK/Nrf2 signaling pathway in DN.

Hirudo Lyophilized Powder Ameliorates Renal Injury in Diabetic Rats by Suppressing Oxidative Stress and Inflammation.

As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.

Effect of tai chi on glycaemic control, lipid metabolism and body composition in adults with type 2 diabetes: A meta-analysis and systematic review.

OBJECTIVE: The aim of this systematic review was to evaluate the effects of tai chi on metabolic control and body composition indicators in patients with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis of existing literature. METHODS: Electronic resource databases were searched to collect eligible studies. Two reviewers selected studies and independently evaluated method-ological quality. RESULTS: Twenty-three studies were included in this meta-analysis. The pooled results showed that tai chi had significant effects in improving metabolic indices, such as fasting blood glucose (mean differ-ence (MD) = -1.04; 95% confidence interval (95% CI) -1.42 to 0.66; p < 0.01) and total cholesterol (MD = -0.50; 95% CI -0.86 to -0.13; p < 0.01) compared with conventional clinical therapy. Most in-dices did not support the use of tai chi over aerobic exercise, except for glycated haemoglobin (HbA1c) (MD = -0.24; 95% CI -0.49 to 0.00; p < 0.01) and high-density lipoprotein (MD = 0.07; 95% CI 0.01 to 0.12; p < 0.01). CONCLUSION: Tai chi had better effects on metabolic control and body composition indicators than clinical conventional therapy, but only on HbA1c and HDL were superior than that of aerobic exercise. The best time-window for tai chi intervention may differ with different metabolic indices.

Clinical characteristics of re-positive COVID-19 patients in Huangshi, China: A retrospective cohort study.

A cluster of patients with coronavirus disease 2019 (COVID-19) underwent repeated positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA tests after they were discharged from the hospital. We referred to them as re-positive (RP) patients in this study. We aimed to describe the clinical characteristics of these patients in a retrospective cohort study. After being treated for COVID-19, the patients underwent 14 days of quarantine following their discharge from the Huangshi Hospital of Traditional Chinese Medicine and the Huangshi Hospital of Youse. Two additional sequential SARS-CoV-2 RNA tests were performed at the end of quarantine. The median age of the 368 patients was 51 years, and 184 (50%) patients were female. A total of 23 RP patients were observed at follow-up. Using multivariate Cox regression analysis, risk factors associated with RP included a higher ratio of lymphocyte/white blood cell on admission (adjusted HR 7.038; 95% CI, 1.911-25.932; P = 0.0034), lower peak temperature during hospitalization (adjusted HR, 0.203; 95% CI, 0.093-0.443; P<0.0001), and the presence of comorbidities, particularly hypertension or chronic diseases in the respiratory system (adjusted HR, 3.883; 95% CI, 1.468-10.273; P = 0.0063). Antivirus treatment with arbidol was associated with a lower likelihood of re-positive outcomes (adjusted HR, 0.178; 95% CI, 0.045-0.709; P = 0.0144).

Acute conduction recurrence of mitral isthmus: Incidence, clinical characteristics, and implications.

BACKGROUND: Data on the incidence, clinical characteristics, and implications of acute conduction recurrence during mitral isthmus (MI) ablation are scarce. METHODS: MI ablation was performed in patients with atrial fibrillation. After confirming bidirectional conduction block, the acute conduction recurrence of MI was systematically evaluated. Clinical and electrophysiological characteristics were analyzed. RESULTS: A total of 66 consecutive patients in whom bidirectional conduction block of MI was achieved were prospectively enrolled in a single center. Acute conduction recurrence of MI developed in 12 (18.2%) patients within 14.2 ± 11.5 minutes after the confirmation of bidirectional conduction block. There were two recurrent conduction breakthrough sites of MI along the course of the great cardiac vein (4.5 ± 3.5 min) in two patients and 11 along the course of the ligament of Marshall (LOM) (16.0 ± 11.6 min, P = .035) in 11 patients. LOM accounted for most (84.6%, 11/13) acute MI conduction recurrence. MI length, total ablation time, and procedure time for MI were greater in patients with acute conduction recurrence than in those without acute conduction recurrence. During follow-up, arrhythmia recurrences were less observed in patients with acute conduction when compared to patients without acute conduction recurrence (0% vs 26.4%, P = .055). CONCLUSION: Acute conduction recurrence, predominantly due to recurrent LOM conduction, was a common phenomenon during MI ablation, and its evaluation should therefore be the focus to improve MI ablation efficacy and durability.

Alpinetin inhibits breast cancer growth by ROS/NF-κB/HIF-1α axis.

Alpinetin, the main active ingredient in the Chinese medicinal herb Alpinia katsumadai Hayata, has been found to have anticancer activity. However, the therapeutic efficacy of signalling cascades modulated by alpinetin remains unknown. Here, we showed that alpinetin provoked mitochondria-associated apoptosis in a dose-dependent manner in breast cancer cells. Mechanistic investigations revealed that alpinetin dampens hypoxia-inducible factor-1α (HIF-1α) signalling due to a lack of NF-κB activation through reduced mitochondrial reactive oxygen species (ROS) production, decreasing HIF-1α transcription. In vivo, we also found alpinetin led to significant tumour regression by inhibiting NF-κB pathway. Overall, our work uncovers a ROS/NF-κB/HIF-1α axis-dependent mechanism underlying the anticancer effects of alpinetin and suggests that alpinetin could act as a novel therapeutic agent against breast cancer.

6-Gingerol exerts anti-inflammatory effects and protective properties on LTA-induced mastitis.

BACKGROUND: Mastitis has a severe impact on human health and breastfeeding. Gram-positive bacteria are one of the most common pathogens, of which lipoteichoic acid (LTA) serves as the main pathogenic factor. Bio-active extractions from herbs is regarded as an alternative method to antibiotics. 6-Gingerol is used for the treatment of tumors and inhibition of inflammation in liver and gallbladder. PURPOSE: To determine whether 6-gingerol can be used as a therapeutic medicine for mastitis. RESULTS: In this article, we used mice as the animal model and RAW264.7/PMECs as cell models. Western blot was for detecting the expression of proteins in NF-κB/MAPK signaling pathways and MMPs/TIMPs. MPO was for the detection of the amount of immune cells. H&E, immunohistochemistry and immunofluorescence were used for locating and detecting the expression of proteins. The detection of inflammatory cytokines was conducted by ELISA and RT-qPCR. We found that the NF-κB/MAPK signaling pathways, formation of ECM, production of inflammatory cytokines and injury to mammary gland cells were attenuated both in vivo and in vitro when 6-gingerol was administered. CONCLUSION: We discovered the function and efficacy of 6-gingerol as a therapeutic compound in LTA-induced mastitis and its probable mechanism of action.

Ginsenoside Rb 1: A novel therapeutic agent in Staphylococcusaureus-induced Acute Lung Injury with special reference to Oxidative stress and Apoptosis.

Acute lung injury (ALI) is considered as an uncontrolled inflammatory response that can leads to acute respiratory distress syndrome (ARDS), which limits the therapeutic strategies. Ginsenosides Rb1 (Rb1), an active ingredient obtained from Panax ginseng, possesses a broad range of pharmacological and medicinal properties, comprising the anti-inflammatory, anti-oxidant, and anti-tumor activities. Therefore, the purpose of the present study was to investigate the protective effects of Rb1 against S. aureus-induced (ALI) through regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial-mediated apoptotic pathways in mice (in-vivo), and RAW264.7 cells (in-vitro). For that purpose, forty Kunming mice were randomly assigned into four treatment groups; (1) Control group (phosphate buffer saline (PBS); (2) S. aureus group; (3) S. aureus + Rb1 (20 mg/kg) group; and (4) Rb1 (20 mg/kg) group. The 20 µg/mL dose of Rb1 was used in RAW264.7 cells. In the present study, we found that Rb1 treatment reduced ALI-induced oxidative stress via suppressing the accumulation of malondialdehyde (MDA) and myeloperoxidase (MPO) and increase the antioxidant enzyme activities of superoxidase dismutase 1 (SOD1), Catalase (CAT), and glutathione peroxidase 1 (Gpx1). Similarly, Rb1 markedly increased messenger RNA (mRNA) expression of antioxidant genes (SOD1, CAT and Gpx1) in comparison with ALI group. The histopathological results showed that Rb1 treatment ameliorated ALI-induced hemorrhages, hyperemia, perivascular edema and neutrophilic infiltration in the lungs of mice. Furthermore, Rb1 enhanced the antioxidant defense system through activating the Nrf2 signaling pathway. Our findings showed that Rb1 treated group significantly up-regulated mRNA and protein expression of Nrf2 and its downstream associated genes down-regulated by ALI in vivo and in vitro. Moreover, ALI significantly increased the both mRNA and protein expression of mitochondrial-apoptosis-related genes (Bax, caspase-3, caspase-9, cytochrome c and p53), while decreased the Bcl-2. In addition, Rb1 therapy significantly reversed the mRNA and protein expression of these mitochondrial-apoptosis-related genes, as compared to the ALI group in vivo and in vitro. Taken together, Rb1 alleviates ALI-induced oxidative injury and apoptosis by modulating the Nrf2 and mitochondrial signaling pathways in the lungs of mice.