Epicoccum sorghinum Causing Leaf Spot on Polygonatum cyrtonema in China.

Polygonatum cyrtonema Hua (family Asparagaceae) is a traditional Chinese medicinal plant that is widely cultivated in various parts of China, including Hunan Province. In summer 2022, a leaf spot disease was observed in 10% of the P. cyrtonema plants (Huang jing) in 18 hectares of this crop in the Hongjiang District (27°18'4″N, 110°11'1″E) of Hunan Province. The initial symptoms of the disease were brown spots on young leaves, and adjacent tissues gradually changed from green to yellow. The entire leaf then became yellow, withered, and eventually exhibited a thn and black appearance. In total, 12 diseased plants from four sampling sites (three plants per site) were collected for laboratory analysis to address the concerns of P. cyrtonema growers. Symptomatic leaf samples were selected, and the leaf fragments containing infected parts of the plants were disinfected with 75% ethanol for 1 min, then immersed in 2.5% hypochlorite for 45 s. After disinfection, symptomatic leaf samples were rinsed three times with sterile water, placed on potato saccharose agar containing 50 µg/ml kanamycin and incubated at 25°C for 2 days. Subsequently, 12 fungal isolates were isolated from various leaf samples through hyphal tip transferring. Ten of the 12 fungal isolates had similar morphological features, and one of them (isolate hjh) was used as the representative isolate for the study. With a growth rate of 6.3 mm per day, its white colonies transformed into red concentric rings in five days; they gradually became black after 10 days of growth. The chlamydospores were round (4.0-9.9 × 3.1-9.3 µm, n = 30), whereas the conidia were ovate (8.0-12.1 × 3.2-6.5 µm, n = 30). The morphological features of the isolate hjh were similar to the features of Epicoccum spp. (Aveskamp et al. 2010). The internal transcribed spacer (ITS) region (including the partial ITS1 sequence and the 5.8S and ITS2 complete sequences), ß-tubulin (tub) gene, and large subunit (LSU) rRNA gene, were amplified from the isolate hjh using the primer pairs ITS5/ITS4, Bt2a/Bt2b, and LROR/LR5, respectively (Taguiam et al. 2021). BLASTn analysis showed that the ITS (OR253745), tub (OR253764), and LSU (OR253746) sequences generated from the isolate hjh were 98-99% similar to the sequences of E. sorghinum strains CBS 179.80 and CBS 627.68. Subsequently, the ITS, tub, and LSU sequences were combined using Sequence Matrix software; phylogenetic analysis via Bayesian and maximum likelihood methods (Vaidya et al. 2011; Li et al. 2021) classified the isolate hjh into the E. sorghinum clade. To fulfill Koch's postulates, pathogenicity tests were conducted on healthy (lesion-free and disease-free) 2-year-old P. cyrtonema plants. Three healthy plants were inoculated by spraying whole plant until run-off with a spore suspension of the isolate hjh (1 × 106 conidia/ml); Three other healthy plants were sprayed with sterile water as controls. The inoculated plants were incubated in a growth chamber at 25 ± 2°C with 85% humidity for 28 days(Chen et al. 2021). Leaves from the inoculated plants gradually became brown within 15 days. Finally, the plants died 28 days after inoculation. The control plants showed no symptoms throughout the experimental period. Isolates (isolate hjh1, hjh2 and hjh3) that were reisolated from the inoculated plants exhibited morphologically similar characteristics and molecularly identical to the original isolate hjh. To our knowledge, this is the first report of E. sorghinum causing leaf spot disease on P. cyrtonema. The results of this study may facilitate the production of P. cyrtonema in China.

Si-Zhi Wan regulates osteoclast autophagy in osteoporosis through the AMPK signaling pathway to attenuate osteoclastogenesis.

OBJECTIVES: The mechanisms underlying the therapeutic effects of Si-Zhi Wan (SZW), a traditional Chinese medicine used to treat osteoporosis (OP), remain unknown. This study investigated the therapeutic effects of SZW on mice that underwent ovariectomy (OVX) and underlying mechanisms thereof. METHODS: We established an in vivo model of OP by performing OVX in mice. Microcomputed tomography (Micro-CT) was used to assess changes in bone characteristics of mice following SZW administration for 4 weeks. H&E staining revealed alterations in bone tissues of mice. Osteoclastogenesis in mouse bone tissue was observed using tartrate-resistant acid phosphatase staining and western blotting. Furthermore, we examined the impact of SZW on osteoclastogenesis in vitro using receptor activator of nuclear factor kappa-B ligand (RANKL). Finally, we explored the regulatory effects of SZW on osteoclast autophagy and the AMPK pathway. KEY FINDINGS: The results demonstrated that high-dose SZW reversed changes in bone density parameters caused by OVX, including bone volume (BV), BV/total volume, trabecular number, and trabecular spacing (P = 0.0007, 0.0035, 0.0114, and 0.0182, respectively), and stimulated the formation of bone trabeculae in mice (P < 0.0001). Furthermore, SZW suppressed osteoclast formation in mice with OVX and inhibited osteoclast formation induced by RANKL. Mechanistically, SZW inhibited osteoclast precursor cell autophagy through the AMPK pathway. CONCLUSIONS: SZW effectively inhibited the autophagy of osteoclast precursors by regulating the AMPK pathway, thereby exerting anti-osteoclastogenic effects and serving as an alternative therapy for OP.

Testosterone regulates thymic remodeling by altering metabolic reprogramming in male rats.

The thymus is an energy-consuming organ, and its metabolism changes with atrophy. Testosterone regulates thymus remodeling (atrophy and regeneration). However, the characteristics of the energy metabolism during testosterone-mediated thymic atrophy and regeneration remain unclear. In this study, we demonstrated that testosterone ablation (implemented by immunocastration and surgical castration) induced global metabolic changes in the thymus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment for differential metabolites and metabolite set enrichment analysis for total metabolites revealed that testosterone ablation affected thymic glycolysis, glutamate metabolism, and fatty acid ß-oxidation. Testosterone ablation-induced thymic regeneration was accompanied by attenuated glycolysis and glutamate metabolism and changed fatty acid composition and content. Testosterone supplementation in immunocastrated and surgically castrated rats enhanced glutaminolysis, reduced the level of unsaturated fatty acids, enhanced the ß-oxidation of unsaturated fatty acids in the mitochondria, boosted the tricarboxylic acid (TCA) cycle, and accelerated thymic atrophy. Overall, these results imply that metabolic reprogramming is directly related to thymic remodeling.

Ethanol extract of Paridis rhizoma attenuates carrageenan-induced paw swelling in rats by inhibiting the production of inflammatory factors.

CONTEXT: Inflammation has been identified as a key factor contributing to the development of numerous diseases. Several anti-inflammatory drugs have been developed to treat inflammation-related diseases. However, some of such drugs are associated with varying degrees of side effects. Therefore, it is imperative to develop new anti-inflammatory drugs with reducing side effects for the treatment of inflammation-related diseases. Natural anti-inflammatory drugs have emerged as an important area of research in recent years. The study was to determine the anti-inflammatory mechanism of Paridis rhizoma extract (PRE) in rat models of acute inflammation induced by carrageenan and RAW264.7 cells models induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: PRE was investigated using the carrageenan-induced paw oedema model on rats in vivo. Histopathology examined the extent of inflammatory infiltration and tissue damage. The effect of PRE on the levels of specific cytokines was determined using enzyme-linked immunosorbent assay (ELISA). The Cell Counting Kit (CCK)-8 assay evaluated the cytotoxic effects of PRE on Raw264.7 cells. The mRNA expression levels of cytokines were quantified using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Western blot measured TNF-α, IL6, TLR4, p-P65, p-IKB, HO1, SOD1 and SOD2. Fluorescence measured the cellular levels of reactive oxygen species (ROS). RESULTS: PRE treatment reduced interstitial edema and structural damage in a dose-dependent manner in vivo. PRE inhibited inflammatory responses in vivo and in vitro, as evidenced by the decreased expression of inflammatory factors, production of ROS, and increased expression of SOD1, SOD2, and HO1. Moreover, PRE inhibited the activity of the nuclear factor kappa B (NF-kB) pathway. CONCLUSION: The anti-inflammatory activity and potential mechanism of PRE were demonstrated according to the results. PRE reduced LPS-induced inflammation in RAW264.7 cells by inhibiting the NF-KB signaling pathway and ROS production in vitro. PRE alleviated interstitial edema and structural damage in the carrageenan-induced paw edema model on rats in vivo. This study provided an idea for future development of PR-based anti-inflammatory drugs.

Guizhi Shaoyao Zhimu granules attenuate bone destruction in mice with collagen-induced arthritis by promoting mitophagy of osteoclast precursors to inhibit osteoclastogenesis.

BACKGROUND: Guizhi Shaoyao Zhimu decoction, a traditional Chinese medicine formula used empirically for the treatment of rheumatoid arthritis (RA), has been shown to alleviate bone destruction in rats with collagen-induced arthritis (CIA). PURPOSE: The aim of this study is to characterize the effects of Guizhi Shaoyao Zhimu granules (GSZGs) on bone destruction in RA and the underlying mechanism. STUDY DESIGN: A CIA arthritis model using DBA/1 mice. The animals were divided into a normal group; CIA model group; low, medium, and high-dose GSZG groups (3, 6, and 9 g/kg/day); and a methotrexate group (1.14 mg/kg/w). In vitro, a cytokine induced osteoclastogenesis model was established. METHODS: After 28 days of treatment, the paw volume was measured, bone destruction was examined by micro-CT, and the generation of osteoclasts in bone tissue was evaluated via tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, the inhibitory effect and underlying mechanism of action of GSZG on RANKL-induced osteoclastogenesis were investigated in vitro. RESULTS: The in vivo analyses demonstrated that the paw volume and degree of bone erosion of mice in the medium- and high-dose GSZG groups were significantly decreased compared to the CIA model group. In addition, GSZG treatment suppressed the excessive generation of osteoclasts in the bone tissue of CIA mice. In vitro, GSZG inhibited RANKL-induced osteoclastogenesis and osteoclast-mediated bone resorption. Specifically, it only inhibited the generation of osteoclast precursors (OCPs); it had no significant effect on the fusion of OCPs or maturation of osteoclasts. Finally, we showed that the inhibitory effect of GSZG on osteoclastogenesis was related to the promotion of PTEN-induced kinase protein 1 (PINK1)/Parkin pathway-mediated mitophagy of osteoclast precursors, which was verified using a PINK1 knockdown small interfering RNA in OCPs. CONCLUSION: These findings indicate that GSZG is a candidate for the treatment of bone destruction in RA and provide a more detailed elucidation of the mechanism of GSZG anti-RA bone erosion, i.e., inhibition of the ROS/NF-κB axis through the PINK1/Parkin-mediated mitochondrial autophagic pathway to inhibit osteoclast precursor production, compared to the published literature.

Multifunctional Nanoplatform-Mediated Chemo-Photothermal Therapy Combines Immunogenic Cell Death with Checkpoint Blockade to Combat Triple-Negative Breast Cancer and Distant Metastasis.

Background: Breast cancer has become the most common cancer in women. Compare with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is more likely to relapse and metastasize. Highly effective therapeutic strategies are desperately needed to be explored. In this study, a multifunctional nanoplatform is expected to mediate chemo-photothermal therapy, which can combine immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis. Methods: Poly (lactic acid-glycolic acid)-Poly (ethylene glycol) (PLGA-PEG) nanoparticles (NPs), a type of polymeric NPs, loaded with IR780, a near-infrared (NIR) dye, and doxorubicin (DOX) as the chemotherapeutic drug, were assembled by an improved double emulsification method (designated as IDNPs). The characterization, intracellular uptake, biosafety, photoacoustic (PA) imaging performance, and biodistribution of IDNPs were studied. Chemo-photothermal therapeutic effect and immunogenic cell death (ICD) were evaluated both in vitro and in vivo. The potency of chemo-photothermal therapy-triggered ICD in combination with anti-PD-1 immune checkpoint blockade (ICB) immunotherapy in eliciting immune response and treating distant tumors was further investigated. Results: IR780 and DOX were successfully loaded into PLGA-PEG to form the IDNPs, with size of 243.87nm and Zeta potential of -6.25mV. The encapsulation efficiency of IR780 and DOX was 83.44% and 5.98%, respectively. IDNPs demonstrated remarkable on-site accumulation and PA imaging capability toward 4T1 TNBC models. Chemo-photothermal therapy demonstrated satisfactory therapeutic effects both in vitro and in vivo, and triggered ICD efficiently. ICD, in combination with anti-PD-1, provoked a systemic antitumor immune response against distant tumors. Conclusion: Multifunctional IDNPs were successfully synthesized to mediate chemo-photothermal therapy, which combines immunogenic cell death with checkpoint blockade to combat TNBC and distant metastasis, showing great promise preclinically and clinically.

Traditional Uses, Phytochemistry, Pharmacology and Toxicology of Rhizoma phragmitis: A Narrative Review.

Rhizoma phragmitis is a common Chinese herbal medicine whose effects are defined as 'clearing heat and fire, promoting fluid production to quench thirst, eliminating irritability, stopping vomiting, and disinhibiting urine'. During the Novel Coronavirus epidemic in 2020, the Weijing Decoction and Wuye Lugen Decoction, with Rhizoma phragmitis as the main herbal component, were included in The Pneumonia Treatment Protocol for Novel Coronavirus Infection (Trial Version 5) due to remarkable antiviral effects. Modern pharmacological studies have shown that Rhizoma phragmitis has antiviral, antioxidative, anti-inflammatory, analgesic, and hypoglycemic functions, lowers blood lipids and protects the liver and kidney. This review aims to provide a systematic summary of the botany, traditional applications, phytochemistry, pharmacology and toxicology of Rhizoma phragmitis.

Oral Chinese Herbal Medicine on Immune Responses During Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

BACKGROUND: Cellular immune responses including lymphocyte functions and immune effector cells are critical for the control of coronavirus infection. Chinese herbal medicine (CHM) potentially has a therapeutic effect for treatment of coronavirus disease 2019 (COVID-19). Nevertheless, there are limited clinical practice suggestions on immunogenicity of the CHM against SARS-CoV-2. To assess the effect of oral CHM on immunogenicity and whether oral CHM improves the clinical parameters through the immunity profile during COVID-19, we performed the present study. METHODS: For this systematic review and meta-analysis, 11 databases were searched for relevant studies assessing oral CHM for COVID-19 on November 20, 2020 (updated March 9, 2021). Primary outcomes mainly included immunity profiles. Secondary outcomes included all-cause mortality; the remission time of fever, cough, chest tightness, and fatigue. The random effect was used to estimate the heterogeneity of the studies. Summary relative risks, weight mean difference and standardized mean difference were measured with 95% confidence intervals. Modified Jadad scale and Newcastle-Ottawa Scale were used to assess the risk of bias of randomized controlled trials (RCTs) and observational studies, respectively. The certainty of evidence was evaluated using the GRADE approach. RESULTS: We analyzed findings from 3,145 patients in 30 eligible studies. Compared with routine treatment, oral CHM, as an adjuvant medicine, improved lymphocyte counts, CD4+, and CD4+/CD8+ ratio with low quality of evidence; improved CD3+ with moderate quality of evidence; and reduced TNF-α with low certainty of evidence. Besides, oral CHM, as an adjuvant medicine reduced the time to clinical symptoms remission with a lower risk of all-cause mortality, compared with routine treatment alone. CONCLUSION: CHM may be recommended as an adjuvant immunotherapy for disease modification and symptom relief in COVID-19 treatment. However, large RCTs objectively assessing the efficacy of CHM on immune responses in COVID-19 are needed to confirm our findings.

Tanshinone II A attenuates vascular remodeling through klf4 mediated smooth muscle cell phenotypic switching.

The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.

[Factors Influencing Mononuclear Cell Collection in Tumor Cell Biotherapy].

OBJECTIVE: To investigate the factors affecting counting and collection efficiency of the final product- mononuclear cells (MNCs) in the collection of mononuclear cells for tumor cell biotherapy. METHODS: The collected data of 142 tumor patients and healthy donors were analyzed, including age, sex, height, weight, BMI, the total blood volume, diagnostic category, vascular access, operator, final product volume, ACD anticoagulant usage, flow rate and circulation times, pre-apheresis Hb, RBC, Plt, WBC, lymphocyte count, monocyte count, neutrophil count, circulating blood volume without anticoagulant, final product MNC and collection efficiency of MNC. CE(collection efficiency)%= final product MNC×100/(pre-apheresis MNC×circulating blood volume without anticoagulant). The factors affecting final products MNC and CE of MNC were detected by T test and multiple linear regression analysis. RESULTS: The CE of tumor patients was higher than that of healthy donors （24.41±1.91,vs 20.01±0.99)，(P=0.043）, and CE of MNC was different among different operators (P=0.01, H=18.59). There was a positive correlation of the final MNC with the volume of final product, ACD anticoagulant usage and pre-apheresis lymphocyte count (P= 0.00, P= 0.01, P= 0.00， r=0.811); CE of MNC negatively correlated with flow rate and pre-apheresis RBC, but positively correlated with operator's working age and ACD anticoagulant usage (P=0.01, P=0.04, P=0.03, P= 0.00, r=0.495). CONCLUSION: more higher pre-apheresis lymphocyte , more amount of the final product and ACD anticoagulant usage, and more high the final MNC. During the collecting process, more ACD anticoagulant usage and more high operator's seniority, lead to the higher MNC'S CE; while more high pre-apheresis RBC and more fast flow rate, cause the lower the CE of MNC.

Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling.

BACKGROUND: Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). METHODS: A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. RESULTS: Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. CONCLUSIONS: LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

Kangfuxin Oral Liquid Attenuates Bleomycin-Induced Pulmonary Fibrosis via the TGF-ß1/Smad Pathway.

Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease with a poor prognosis characterized by transforming growth factor (TGF)-ß-induced proliferation, migration, and differentiation of fibroblasts, resulting in excessive extracellular matrix (ECM) deposition. Whether Kangfuxin oral liquid (KFXOL) has a protective function in pulmonary fibrosis is largely unknown. The goal of this study was to investigate the potential efficacy of KFXOL, as well as the underlying mechanism by which KFXOL regulates pulmonary fibrosis in vivo and in vitro. We found that KFXOL dramatically attenuated intratracheal bleomycin (BLM)-induced pulmonary fibrosis in terms of both severe alveolar architecture destruction and collagen deposition. KFXOL treatment significantly inhibited the proliferation, migration, and differentiation of pulmonary fibroblasts following activation using BLM/TGF-ß1 and normalized the expression of ECM deposition-related proteins, including matrix metalloproteinase (MMP)-1, MMP-9, and tissue inhibitor of metalloproteinases 1. These effects were mediated via the inhibition of TGF-ß1 and phosphorylated Smad2/3 activation in vivo. Taken together, our data suggest that KFXOL attenuates the development of pulmonary fibrosis via the TGF-ß1/Smad signaling pathway and thus has potential utility in the treatment of pulmonary fibrosis.

Inhibiting the formation of advanced glycation end-products by three stilbenes and the identification of their adducts.

The objective of this work is to investigate the inhibition effects on AGEs formation and the ability of scavenging toxic carbonyls of three stilbenes, resveratrol, oxyresveratrol, and piceatannol. The results showed that the three stilbenes had the activity to inhibit the AGEs formation in BSA-acrolein and BSA-methylglyoxal models, especially piceatannol which showed the strongest inhibition effects on the formation of AGEs with the half maximal inhibitory concentrations (IC50) value of 2.44 mM and 0.19 mM in the BSA-acrolein and BSA-methylglyoxal model, respectively. In addition, the three stilbenes showed the ability to scavenge acrolein and methylglyoxal in pH 7.4 at 37 °C. Eight isolated adducts between three stilbenes and toxic carbonyls further confirmed that these three stilbenes could scavenge acrolein and methylglyoxal by forming adducts successfully. Thus, the present study suggested that the consumption of foods containing stilbenes was beneficial for controlling the amount of reactive carbonyl species and the AGEs formation.

Effects of mutual grafting on the cadmium accumulation characteristics of two ecotypes of Solanum photeinocarpum.

The effects of mutual grafting on the cadmium (Cd) accumulation characteristics of two ecotypes (farmland and mining) of the potential Cd-hyperaccumulator Solanum photeinocarpum were studied through a pot experiment for one month. Four treatments were used in the experiment: ungrafted farmland ecotype (F-CK), ungrafted mining ecotype (M-CK), the farmland ecotype as the scion grafted onto rootstocks of the mining ecotype (F-Scion), and the mining ecotype as the scion grafted onto rootstocks of the farmland ecotype (M-Scion). Mutual grafting increased the rootstock biomass of both S. photeinocarpum ecotypes. However, mutual grafting decreased the scion biomass of F-Scion compared with F-CK and M-CK, and the scion biomass of M-Scion was higher than that of M-CK and lower than that of F-CK. The Cd content in the rootstock of M-Scion increased compared with F-CK, and the Cd content in the rootstock of F-Scion increased compared with M-CK, but mutual grafting decreased the Cd content in scions of both S. photeinocarpum ecotypes. Mutual grafting increased Cd extraction by rootstocks of both S. photeinocarpum ecotypes, but decreased extraction by scions. Therefore, mutual grafting can increase Cd accumulation in S. photeinocarpum rootstocks but not increase Cd accumulation in S. photeinocarpum scions in a short period.

Gut microbiota was modulated by moxibustion stimulation in rats with irritable bowel syndrome.

BACKGROUND: The pathogenesis of irritable bowel syndrome (IBS) is closely related to intestinal dysbacteriosis and can be controlled by moxibustion treatment. However, the mechanism underlying the therapeutic value of moxibustion in IBS treatment remains unknown. METHODS: An IBS rat model was established by colorectal distention (CRD) stimulus and mustard oil clyster. Sixty-five male rats were randomly divided into six groups: normal, IBS model, moxibustion, electroacupuncture (EA), Bifid-triple Viable Capsule (BTVC) and Pinaverium Bromide (PB) groups. The moxibustion group was treated with mild moxibustion at the bilateral Tianshu (ST25) and Shangjuxu (ST37) for 10 min/day for 7 days, the EA group was given EA at ST25 and ST37 once daily for 7 days, while the BTVC group and PB groups received Bifid-triple Viable Capsule and Pinaverium Bromide solution (at the proportion of 1:0.018) respectively by gavage once daily for 7 days. After the treatment, abdominal withdrawal reflex (AWR) scores were determined based on CRD stimulus, gut microbiota profiling was conducted by 16S rRNA high-throughput sequencing. RESULTS: Irritable bowel syndrome model rats had significantly increased AWR scores at all intensities (20, 40, 60 and 80 mmHg) compared with the normal group. Moxibustion treatment significantly reduced AWR scores compared with the IBS model group at all intensities. Across all groups the most abundant phyla were Bacteroidetes and Firmicutes followed by Proteobacteria and Candidatus Saccharibacteria. At genus level IBS model rats had a higher abundance of Prevotella, Bacteroides and Clostridium XI and a lower abundance of Lactobacillus and Clostridium XIVa compared with normal rats. These changes in microbiota profiles could however be reversed by moxibustion treatment. Alpha diversity was decreased in IBS model rats compared with normal rats, yet significantly increased in moxibustion- and PB-treated rats compared with IBS rats. CONCLUSION: Our findings suggest that moxibustion treats IBS by modulating the gut microbiota.

Establishment of a human intrapleural hyperthermic perfusion model and analysis of pleural malignancy treatment depth.

INTRODUCTION: Although human intrapleural hyperthermic perfusion (HIHP) has achieved excellent palliative effects in metastatic pleural malignancies, the optimum treatment conditions, including inlet temperature and treatment times based on tumor size, have yet to be determined. However, such information is recognized to be critical for treatment planning in clinics. Therefore, the current research aimed to solve these issues. METHODS: Using the finite-element method (FEM), a simplified three-dimensional HIHP model was established and verified according to the temperature data of specific measuring points based on a clinical therapeutic case. Ultimately, the treatment depth of pleural malignancies was obtained by employing an equivalent thermal dose of 80 min as the damage threshold. RESULTS: The treatment depth of parietal pleural malignancies (PPM) is much larger than that of visceral pleura malignancies (VPM), and can therefore be overlooked. In addition, the average treatment depth of the PPM increased by 1 mm as treatment time increased by 30 min during the 60-120 min time frame and as the inlet temperature increased by 1 °C, while there was no further increase when treatment time exceeded 120 min. CONCLUSIONS: HIHP can provide superior treatment for PPM and only provided faintly therapeutic effects on VPM, and may not be appropriate for the larger VPM. Although we only studied one example in this article, this is the beginning of an intensive study into the detailed thermal behavior of pleural tissues under HIHP, and further analysis on more realistic cases is currently underway.

Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock.

LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10mg/kg) or DEX (5mg/kg) at 1 and 12h before injecting LPS (30mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway.

Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) is a life-threatening disease characterized by serious lung inflammation and increased capillary permeability, which presents a high mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus, has been reported to have definite anti-bacterial, anti-oxidant, and anti-inflammatory activities. However, the effects of IF against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of IF against LPS-induced ALI in mice. In this study, We found that pretreatment with IF significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also found that total cells, neutrophils and macrophages in BALF, MPO activity in lung tissues were markedly decreased. Besides, IF obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that IF has a protective effect against LPS-induced ALI, and the protective effect of IF seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2.

[Analysis of Volatile Components of Polypodium hastatum by GC-MS].

OBJECTIVE: To further reveal the chemical constituents of Polypodium hastatum, volatile components from this plant were investigated. METHODS: The volatile components were extracted under reflux from the whole plant of Polypodium hastatum, and then analyzed qualitatively and quantitatively by GC-MS. RESULTS: 60 volatile components were detected and of all components detected, the structures and relative contents of 34 volatile compounds were elucidated. CONCLUSION: In the volatile components identified, most are fatty acid esters, especially methyl and ethyl esters, which compose the major volatile chemical constituents of Polypodium hastatum.

Protective effects of esculentic acid against endotoxic shock in Kunming mice.

Esculentic acid (EA), a triterpene compound extracted from the root of Phytolacca esculenta (the Chinese name Shang Lu), has been widely used to therapy a variety of inflammatory diseases such as rheumatoid arthritis, edema, hepatitis and bronchitis. The present study was designed to investigate the protective effects of EA against LPS-induced endotoxic shock by the intraperitoneal injection of EA (1, 5 and 10 mg/kg) prior to LPS stimulation (1 mg/kg, i.p.). We examined the effects of EA on the survival rate of mice, inflammatory cytokine and pro-inflammatory mediator production, histopathological changes and protein expression of COX-2 in tissue sections from lung, liver and kidney. The results indicate that EA not only increases the survival rate of mice, but decreases the levels of TNF-α, IL-6, NO and PGE2 in serum or tissues, histopathological changes and COX-2 protein expression also. Furthermore, EA also increases the levels of anti-inflammatory cytokine IL-10 in serum. Overall, these data suggest that the protective effects of EA against LPS-induced endotoxic shock may be mediated, at least in part, by regulation the release of inflammatory cytokines and mediators, and protein expression of COX-2 in mice.