Treatment of diabetic foot with moxibustion: Clinical evidence from meta-analysis.

To assess the efficacy of moxibustion for diabetic foot, and compile the findings of randomised clinical trials. China National Knowledge Infrastructure Database, Medicine, WanFang Database, Embase, Chinese Scientific Journal Database and Web of Science were from the establishment to January, 2024 were searched. Randomised controlled trials, which evaluated the effects of moxibustion were included. A total of 12 randomised controlled trials involving 1196 patients were included. According to the pooled results of this meta-analysis, effective rate (relative risk 1.16, 95% confidence intervals, CI [1.11, 1.22]), healing time (mean difference [MD] -6.27, 95% CI [-8.68, -3.86]), wound area (MD 3.46, 95% CI [0.84, 6.09]), and ankle brachial index (MD 0.14, 95% CI [0.03, 0.24]) were statistically significant compared to the control group. This study suggests that moxibustion treatment has the potential for improving symptoms of diabetic foot. However, future in-depth research on the benefits and harms of moxibustion for the diabetic foot is needed before it can be accepted as an evidence-based treatment.

Kaempferol prevents angiogenesis of rat intestinal microvascular endothelial cells induced by LPS and TNF-α via inhibiting VEGF/Akt/p38 signaling pathways and maintaining gut-vascular barrier integrity.

Kaempferol is a major flavonoid found in natural plant extracts; it shows great potential in anti-inflammatory and anti-cancer medicine. However, the underlying mechanism of the protective action of kaempferol on the gut-vascular barrier (GVB) and the active sites preventing intestinal micro-angiogenesis has not been reported. The purpose of our study is to investigate the protective effect of kaempferol on the barrier damage induced by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α), and its mechanism of protective action on intestinal micro-angiogenesis. Our data showed that the combination of LPS and TNF-α activates the inflammatory response of the rat intestinal microvascular endothelial cells (RIMVECs), leading to overexpression of vascular endothelial growth factors (VEGFs). Also, the permeability of GVB and transepithelial electrical resistance (TEER) constructed by Transwell and the tubular structure of RIMVEC were significantly affected. Kaempferol (25, 50, and 100 µM) decreased the inflammatory factor secretion and GVB permeability, down-regulated the expression of VEGFs, p-Akt, and hypoxia-inducible factor-1alpha (HIF-1α). It also alleviated the abnormal expression of tight junction proteins (TJs). Moreover, kaempferol may prevents intestinal angiogenesis in the presence of Akt inhibitor (MK-2206 2HCl) by regulating tube formation and downstream signaling of the VEGF/Akt pathways. In addition, the wound healing test showed that kaempferol had a similar effect in the presence of p38 inhibitor (SB203580), which intuitively restrained the migration of RIMVECs and reduced the p38 MAPK signaling. Our results demonstrated that kaempferol exhibits significant anti-inflammatory effects in LPS and TNF-α induced inflammatory environments. Kaempferol prevents intestinal angiogenesis by impeding the tube formation and migration of RIMVECs. It also suppresses the expression of angiogenesis-related signals, thereby protecting the GVB.

Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4/NF-κB/NLRP3 signaling pathway in vivo and in vitro.

Background: Inflammatory bowel diseases are characterized by the alterations of the mucosa and gastrointestinal physiology, and the core of these alterations is endothelial cells. Quercetin is a flavonoid presents in some traditional Chinese medicine, plants, and fruits. Its protective effects in several gastrointestinal tumors have been demonstrated, but its effects on bacterial enteritis and pyroptosis-related diseases have rarely been studied. Objective: This study aimed to evaluate the effect of quercetin on bacterial enteritis and pyroptosis. Design: In vitro experiments were performed using rat intestinal microvascular endothelial cells divided into seven groups: control group (no treatment), model group (10 µg/mL lipopolysaccharide (LPS)+1 mM adenosine triphosphate [ATP]), LPS group (10 µg/mL LPS), ATP group (1 mM ATP), and treatment groups (10 µg/mL LPS+1 mM ATP and 5, 10, and 20 µM quercetin). The expression of pyroptosis-associated proteins, inflammatory factors, tight junction proteins, and the percentage of late apoptotic and necrotic cells were measured. In vivo analysis was performed using specific pathogen-free Kunming mice pretreated with quercetin and the water extract of Cacumen Platycladi for 2 weeks followed by 6 mg/kg LPS on day 15. Inflammation in the blood and intestinal pathological changes were evaluated. Results: Quercetin used in vitro significantly reduced the expression of Toll-like receptor 4 (TLR4), NOD-like receptor 3 (NLRP3), caspase-1, gasdermin D, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor-α. It also inhibited phosphorylation of nuclear factor-kappa B (NF-κB) p65 and increased cell migration and the expression of zonula occludens 1 and claudins, while reduced the number of late apoptotic cells. The in vivo results showed that Cacumen Platycladi and quercetin significantly reduced inflammation, protected the structure of the colon and cecum, and prevent fecal occult blood induced by LPS. Conclusions: These findings suggested the ability of quercetin to reduce inflammation induced by LPS and pyroptosis through TLR4/NF-κB/NLRP3 pathway.

TB@PLGA Nanoparticles for Photodynamic/Photothermal Combined Cancer Therapy with Single Near-Infrared Irradiation.

BACKGROUND: Phototherapy has significant potential as an effective treatment for cancer. However, the application of a multifunctional nanoplatform for photodynamic therapy (PDT) and photothermal therapy (PTT) at a single excitation wavelength remains a challenge. MATERIALS AND METHODS: The double emulsion solvent evaporation method was used to prepare toluidine blue@poly lactic-co-glycolic acid (TB@PLGA) nanoparticles (NPs). The biocompatibility of TB@PLGA NPs was evaluated, and a 660 nm luminescence was used as the light source. The photothermal effect, photothermal stability, and singlet oxygen yield of NPs in an aqueous solution verified the feasibility of NPs as a PTT/PDT synergistic therapy drug. RESULTS: TB@PLGA NPs were successfully prepared and characterized. In vitro experiments demonstrated that TB@PLGA NPs can cause massive necrosis of tumor cells and induce apoptosis through a photodynamic mechanism under 660 nm laser irradiation. The TB@PLGA NPs also achieved optimal tumor inhibition effect in vivo. CONCLUSION: The TB@PLGA NPs prepared in this study were applied as a dual-mode phototherapeutic agent under single laser irradiation. Both in vitro and in vivo experiments demonstrated the good potential of PTT/PDT for tumor inhibitors.

Coix Seed Diet Ameliorates Immune Function Disorders in Experimental Colitis Mice.

Coix seed is a functional food in the Chinese diet that possesses the ability to alleviate ulcerative colitis clinically. However, the underlying mechanisms remain ambiguous. In this study, we investigated the protective effect of the Coix seed diet on experimental colitis mice. The mice were randomly divided into four groups: control group, model group, Coix seed feed group, and positive control group. The maintenance feed of the mice was replaced with Coix seed feed 10 days before orally administering the mice 5% (w/v) dextran sulfate sodium drink. As a result, the Coix seed feed alleviated colitis symptoms, maintained the complete blood count at a normal level, reduced the pathological score, relieved inflammatory cytokine secretion, and alleviated oxidative stress. Network pharmacology analysis was used for further exploration of the targets of Coix seed feed. The results showed that T-cell regulation is one of the targets of Coix seed feed, and the analysis of the T-lymphocyte subset and innate immune cell distribution of the colon tissue supported the network pharmacology results. In conclusion, Coix seed, as a staple food, can alleviate experimental colitis, and the mechanism may be related to the immune regulation effect of Coix seeds.

Historical Facts of Acupuncture and Traditional Chinese Veterinary Medicine-A Letter to the Editor Re: Magalhães-Sant'Ana, M. Animals 2019, 9, 168.

A recent viewpoint paper by Manuel Magalhães-Sant'Ana (2019) discussed the evidence regarding history, conceptions and modern research related to Traditional Chinese Veterinary Acupuncture (TCVA). Based on the observation of an illustration of nine needles, the author suggested that the needles used in acupuncture are more like lancets than needles in ancient times; to support the view that acupuncture is analogous to bloodletting. In addition; the author does not believe that TCVA has not been practiced for thousands of years. This letter documents that the prototype of the modern filiform acupuncture needle has appeared as early as the Han Dynasty and that modern needles did not evolve from lancets. In addition, there is proof based on existing ancient books that TCVA has a history of thousands of years.

Huai hua san alleviates dextran sulphate sodium-induced colitis and modulates colonic microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Huai hua san (HHS) is a traditional Chinese herbal formula which is firstly documented in the ancient Chinese classic medical work "Pu Ji Ben Shi Fang" in 1132 AD. It has been widely used in the treatment of lower gastrointestinal disorders such as acute colitis and hematochezia for more than 800 years. However, scientific evidence of the efficacy and the exact mechanism of HHS against colitis has not yet been reported. AIM OF THE STUDY: The aim of this study is to investigate the potential effects of HHS in the alleviation of dextran sulphate sodium (DSS)-induced colitis and the alteration of colonic microbiota composition and structure. MATERIALS AND METHODS: HHS solution was orally administrated to 5% DSS-challenged rats once a day for 8 days. Colitis clinical symptoms of colitis were collected, together with colonic mucosal damage assessed at histomorphometric and ultrastructural levels. The protein levels of inflammatory mediators TNF-α and CRP were detected by ELISA. The colonic vascular permeability was evaluated by Evans blue extravasation. Meanwhile, The effects of the HHS therapy on the colonic microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. RESULTS: Daily oral administration of HHS markedly alleviated DSS-induced colitis, as evidenced by decreased colitis disease activity index (DAI) score, reduced colonic inflammation and normalization of colonic vascular hyperpermeability. Moreover, the 16S rRNA gene sequencing analysis demonstrated that HHS treatment during colitis prevented the colitis-associated alteration of colonic microbial community at operational taxonomic unit level, together with the DSS-induced colonic microbiota dysbiosis at taxonomic levels. In addition, HHS therapy reduced colitis-associated high increased ratio of Bacteroidetes to Firmicutes to a normal level. CONCLUSION: HHS could attenuate ulcerative colitis and ameliorate gut microbial dysbiosis.

Protective Effect of Naringin on In Vitro Gut-Vascular Barrier Disruption of Intestinal Microvascular Endothelial Cells Induced by TNF-α.

Naringin is a polymethoxylated flavonoid commonly found in citrus species and has therapeutic potential in intestinal disorders. However, the effect and mechanism of naringin on gut-vascular barrier disruption has not yet been reported. This study aimed to investigate the distinguishing and selectively protective effects of naringin on tumor necrosis factor (TNF)-α-induced gut-vascular barrier disruption and elucidate the potential mechanism. In the present study, an in vitro gut-vascular barrier model composed of rat intestinal microvascular endothelial cells (RIMVECs) was studied. Evans blue-albumin efflux assay showed that naringin (50 µM) evidently protected the integrity of RIMVEC monolayer barriers against TNF-α-induced disruption. Naringin maintained the expression and distribution of tight junction proteins including zona occludin-1, occludin, claudin-1, and claudin-2. Additionally, naringin protected RIMVECs from TNF-α-induced apoptosis and cell migration suppression (41.1 ± 2.2 vs 51.1 ± 3.5%; 61.0 ± 5.1 vs 72.2 ± 6.2%). Our results indicate that naringin effectively ameliorates gut-vascular barrier disruption.

Modulation of the Gut Microbiota by Shen-Yan-Fang-Shuai Formula Improves Obesity Induced by High-Fat Diets.

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Shen-Yan-Fang-Shuai formula (SYFSF) is a traditional Chinese herbal formula composed of Astragali Radix, Radix Angelicae Sinensis, Rheum Officinale Baill, and four other herbs. In this study, we identified that SYFSF treatment prevented weight gain, low-grade inflammation and insulin resistance in high-fat diet (HFD)-fed mice. SYFSF also substantially improved gut barrier function, reduced metabolic endotoxemia, as well as systemic inflammation. Sequencing of 16S rRNA genes obtained from fecal samples demonstrated that SYFSF attenuated HFD-induced gut dysbiosis, seen an decreased Firmicutes to Bacteroidetes ratios. Microbial richness and diversity were also higher in the SYFSF-treated HFD group. Furthermore, similar therapeutic effects and changes in gut microbiota profile caused by SYFSF could be replicated by fecal microbiota transfer (FMT). Taken together, our study highlights the efficacy of SYFSF in preventing obesity and related metabolic disorders. Its therapeutic effect is associated with the modulation of gut microbiota, as a prebiotic.

Rhein from Rheum rhabarbarum Inhibits Hydrogen-Peroxide-Induced Oxidative Stress in Intestinal Epithelial Cells Partly through PI3K/Akt-Mediated Nrf2/HO-1 Pathways.

Rheum rhabarbarum has been widely used as a herbal medicine and food in China. The objective of this study was to investigate the cytoprotective action and underlying mechanisms of rhein, one active ingredient isolated from R. rhabarbarum, on H2O2-challenged rat small intestine epithelial cells (IEC-6 cells). H2O2-challenged IEC-6 cells were incubated in the pretreatment with or without rhein or LY294002, a PI3K/Akt inhibitor. The cell viability, apoptosis, intracellular reactive oxygen species (ROS), and antioxidants were measured. The expressions of heme oxygenase 1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), Akt, and p-Akt were evaluated by western blotting. Meanwhile, LY294002 was also used to investigate the role of PI3K/Akt in the rhein-induced cytoprotective role. The results showed that pretreatment of rhein could reverse the inhibition of cell viability and suppress the apoptosis, caspase-3 activity, and intracellular ROS induced by H2O2. Rhein also supported SOD activity catalase activity, glutathione S-transferase activity, and glutathione content. Furthermore, rhein induced the protein expression of HO-1 together with its upstream mediator Nrf2 and activated the phosphorylation of Akt in IEC-6 cells. LY294002 inhibited increased cell viability, upregulated the lowered apoptotic rate, and enhanced the weakened ROS levels. Although the inhibition of PI3K/Akt did not inhibit the Nrf2 nuclear level under 4 µM rhein, LY294002 inhibited the Nrf2 nuclear level under 2 µM rhein and blocked HO-1 expression. These data demonstrated that rhein protected IEC-6 cells against oxidative damage partly via PI3K/Akt and Nrf2/HO-1 pathways.

Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway.

Tetrahydroxystilbene glucoside (TSG) is a unique component of the bone-reinforcing herb Radix Polygoni Multiflori Preparata (RPMP). It has the ability to promote bone formation and protect osteoblasts. However, the underlying mechanism remains unclear. To better understand its biological function, we determined TSG's effect on murine pre-osteoblastic MC3T3-E1 cells by the MTT assay, flow cytometry, FQ-PCR, Western blot, and ELISA. The results showed that TSG caused an elevation of the MC3T3-E1 cell number, the number of cells in the S phase, and the mRNA levels of the runt-related transcription factor-2 (Runx2), osterix (Osx), and collagen type I α1 (Col1a1). In addition, the osteoprotegerin (OPG) mRNA level was up-regulated, while the nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) mRNA levels were down-regulated by TSG. Furthermore, TSG activated the phosphoinosmde-3-kinase/protein kinase B (also known as PI3K/Akt) pathway, and blocking this pathway by the inhibitor LY-294002 could impair TSG's functions in relation to the MC3T3-E1 cells. In conclusion, TSG could activate the PI3K/Akt pathway and thus promote MC3T3-E1 cell proliferation and differentiation, and influence OPG/RANKL/M-CSF expression. TSG merits further investigation as a potential therapeutic agent for osteoporosis treatment.

Changes of Anthocyanin Component Biosynthesis in 'Summer Black' Grape Berries after the Red Flesh Mutation Occurred.

The coloring process of grape flesh is valuable for research and promotion of the high nutritional quality of anthocyanins. 'Summer Black' and it is new red flesh mutant were used to analyze the changes of anthocyanin biosynthesis during grape berry development. Eighteen kinds of anthocyanins were detected in mature berries of the two cultivars, but the content of most 3'- and 3',5'-substituted anthocyanins was higher in the skin of the mutant. Anthocyanin accumulation occurred simultaneously in the skin and flesh of the mutant, and their types and content were more abundant in the former. For the mutant, there were only CHS, OMT, MYBA3, and MYBPA1 at lower transcriptional level in the flesh during veraison when compared with these in the skin, which might be an important factor to limit the anthocyanin accumulation in the flesh. The occurrence of red flesh might be related the enhancement of anthocyanin biosynthesis in the whole berry.

Effect of Fructus Ligustri Lucidi on osteoblastic like cell-line MC3T3-E1.

UNLABELLED: Fructus Ligustri Lucidi, fruits of Ligustrum lucidum Ait. (Oleaceae), has the effects of tonifying the liver and the kidney and strengthening the bones and muscles. In ancient times, Fructus Ligustri Lucidi can be prepared in ethanol or in water. Some active compounds have been found in Fructus Ligustri Lucidi, like Oleanolic acid and Ursolic acid, and Ursolic acid were proved to have osteogenic effects. METHODS AND RESULTS: To prove that Fructus Ligustri Lucidi water extract have osteogenic effects on MC3T3-E1 cells and how these effects work, we used CCK-8 (cell counting kit-8), ELISA (enzyme-linked immunosorbent assay), FQ-PCR (realtime fluorescence quantitative PCR) and western blot assays. After treatment with Fructus Ligustri Lucidi for 48h, 72h, 96h, the cell viability was marked increased, on concentration-dependently and time-dependently pattern. High and low concentrations of Fructus Ligustri Lucidi promoted differentiation of cells. Fructus Ligustri Lucidi could up-regulate OPG and RANKL protein in supernatant at 48h and 72h except for highest concentration (10(-1)mg/ml). Fructus Ligustri Lucidi promote OPG and RANKL mRNA expression at 48h and 72h, while the level of promoting at 72 was higher than 48h. 10(-5)mg/ml of Fructus Ligustri Lucidi up-regulates OPG protein expression and down-regulates RANKL protein expression. After treatment with Fructus Ligustri Lucidi water extract, inhibitors, Fructus Ligustri Lucidi water extract with inhibitors for 72h, inhibitors PD 98059, SB 203580, SP600125 and LY 294002 showed Fructus Ligustri Lucidi-induced cell proliferation and the leakage of OPG proteins effects. Fructus Ligustri Lucidi promoted the protein levels of ERK, p-ERK, p-JNK, p38, pp38, AKT and p-AKT, and inhibited the protein levels of JNK. CONCLUSIONS: Fructus Ligustri Lucidi water extract promoted cell proliferation and differentiation, mRNA and protein expression of OPG and RANKL on MC3T3-E1 cells. The effects of cell proliferation and leakage of OPG related to MAPK and AKT signaling pathways in different ways.

Impact of matrine on inflammation related factors in rat intestinal microvascular endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Matrine (MT) is a main active ingredient of Sophora flavescens roots, which is used in Traditional Chinese Medicine (TCM) for the treatment of inflammations like enteritis, hepatitis and atopic dermatitis. AIMS OF THE STUDY: Aim of the study is to gain insight into the effects of MT on nitric oxide (NO) release, intracellular NO production, and endothelial nitric oxide synthase (eNOS) level in second generation rat intestinal microvascular endothelial cells (RIMECs). Moreover, the effects of MT on soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) production induced by lipopolysaccharide (LPS) in these cells were evaluated. MATERIAL AND METHODS: Isolated and identified RIMECs cultures were exposed to different concentrations of matrine, and changes in extra- and intracellular NO concentrations were measured in dependance of time by Griess reaction or DAF-FM diacetate. Obtained cell cultures were solitude treated with lypopolysaccharide (LPS) or combined with MT to observe impacts on sICAM-1, IL-6 and IL-8 concentration in culture supernatants by ELISA. RESULTS: Matrine dose-dependently increased the concentration of NO in culture supernatant of RIMECs. Exposure of MT resulted in a steady intracellular NO increase pattern under different concentrations with different values and has an increasing effect on eNOS concentration at a long time exposure. Additionally, matrine reduced the increasing effect of LPS on the production of IL-6, IL-8, and sICAM-1 in RIMECs. CONCLUSION: These results show that matrine may serve as a protective agent against tissue damage in inflammation by improving NO-dependent vasomotion and inhibiting inflammatory cytokines induced by LPS.

[Observation on therapeutic effect of blood-letting therapy on apoplectic hemiplegia numbness syndrome].

OBJECTIVE: To observe therapeutic effect of blood-letting therapy on apoplectic hemiplegia numbness syndrome and search for clinically effective therapy. METHODS: Ninety and five cases of apoplectic hemiplegia were randomly divided into a treatment group of 55 cases and a control group of 40 cases in order of visiting. The treatment group were treated with tapping Huatuo Jiaji (EX-B2) on the back by plum-blossom needle combined with blood-letting on twelve Well-points or Shixuan (EX-UE 11), once every day, 6 times constituting one course; the control group were treated with routine acupuncture at points of the four limbs, once daily, 12 times constituting one course. After they were treated for 4 courses, their therapeutic effects were observed. RESULTS: The total effective rate was 94.5% in the treatment group and 77.5% in the control group with a significant difference between the two groups (P < 0.01). CONCLUSION: Blood-letting therapy is an effective therapy for post-apoplectic hemiplegia numbness syndrome.