Cutaneous nodular polyarteritis presenting as refractory ulcers on both lower extremities: A case report.

BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a systemic disease that is limited to the skin. cPAN usually presents with cutaneous reticular cyanotic, erythematous and palpable nodules, and cutaneous ulcers.Research has indicated that the use of hormones and immunosuppressive drugs can delay ulcer healing and associated neuropathy, and also elevate the risk of disease recurrence upon their reduction or withdrawal. Therefore, it is a necessary to find a safe and effective approach that minimize hormone side effects in ulcer treatment. CASE PRESENTATION: The patient, a 48-year-old female of Han Chinese ethnicity, has suffered from recurrent erythema nodosum on both lower limbs for 8 years. The condition was aggravated by skin breakdown over the last 3 months. Despite multiple treatments, the patient's condition did not improve significantly, leading to the exploration of a combined approach of traditional Chinese and Western medicine. Following six months of combined traditional Chinese and Western medicine treatment, t the patient's newborn erythema and ulcers on both lower limbs did not reappear, and the ulcers gradually decreased in size and the erythema disappeared. The patient took the TCM regularly until April 15, 2023, when the ulcers were completely healed. Three months after the patient stopped taking TCM, the ulcers had completely healed with no recurrence, as observed during the follow-up visit on July 14th, 2023. CONCLUSION: Traditional Chinese Medicine Combined with Low-Dose Hormones May Effectively Treat Bilateral Lower Extremity Skin Ulcers Caused by Cutaneous Polyarteritis Nodosa.

Ruan Jian Qing Mai's Formula Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration and Proliferation.

Objective: To investigate the response of (BM-MSCs) to the Ruan Jian Qing Mai formula (RJQM) in the treatment of atherosclerotic occlusion (ASO), and consequently promoting the development of collateral circulation and angiogenesis. Method: 35 male rats were randomly assigned to 6 experimental groups and A control group. 0.9% NaCl solution and 2.7, 5.4, 10.8, 16.2, 21.6, and 27 g × kg-1 × d-1 of RJQM formula were gavaged to the experimental groups twice a day for 8 days. After the last administration, medicated serum was prepared from the blood collected from the abdominal aorta. The human BM-MSCs were divided into an experimental group and a control group. A blank group of cells was added with a complete medium without rat serum; an experimental group of cells was added with the prepared drug-containing serum. Under hypoxic conditions, the drug-containing serum was used to treat BM-MSCs and/or endothelial cells of human umbilical vein (HUVECs). A Cell counting kit (CCK8) was used to detect cell proliferation. Western blot (WB) and quantitative real-time PCR (qPCR) were used to identify related genes expression. Results: The results of this study showed that the purity of the BM-MSCs was >95%. The drug-containing serum significantly rise in CCND1 expression (encoding cyclin D1) and MYC, especially when the concentration of medicated serum was 10.8 g × kg-1 × d-1. Treatment of either BM-MSCs or HUVECs alone or both with medicated serum aids in the spread of mesenchymal stem cells from the bone marrow to HUVECs. qPCR results showed that the mRNA expression of CCL2, CCL3, CCL25, IL8, IGF1, and PDGFB increased dramatically after treatment with medicated serum. The expression of the corresponding receptors for these up-regulated chemokines was detected in BM-MSCs, and it was found that CXCR1, CXCR4, CXCR7, and PDGFRB were up-regulated. Conclusion: This study provides a preliminary understanding of the mechanism of RJQM in the treatment of ASO.

Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.

Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.

Jingfang Granules improve glucose metabolism disturbance and inflammation in mice with urticaria by up-regulating LKB1/AMPK/SIRT1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Granule (JFG) is a Traditional Chinese Medicine prescription to empirically treat skin disease such as urticaria in clinical practice. However, the potential mechanisms of JFG on urticaria are not fully defined. AIM OF STUDY: The aim of this study is to investigate the mechanisms of JFG in treating urticaria through an OVA/aluminum hydroxide induced urticaria mice model. MATERIALS AND METHODS: KM mice were injected intraperitoneally (i.p.) with OVA/aluminium hydroxide to establish the model with urticaria. After the mice were administered JFG, itching degree and hematoxylin and eosin (H&E) staining were used to assess the protective effect of JFG on mice with urticaria. The regulatory networks were investigated by proteomics and central carbon metabolomics. Spleen T lymphocyte subsets were detected by flow cytometry. Peripheral blood cytokines were detected using ELISA kits or Cytometric Bead Array (CBA) kits. The protein expression of skin tissue was detected by western blot or immunohistochemical staining. RESULTS: JFG significantly relived skin tissue lesions and skin pruritus in mice with urticaria. Meanwhile, JFG significantly decreased IgE, IL-1ß, IL-6, IL-4, TNF-α and IL-17A levels and increased IFN-γ levels in the serum of urticaria mice by inhibiting the expression of inflammation associated proteins including TLR4 and p-NF-κB p65, p-ERK1/2, p-JNK and p-p38, NLRP3, ASC and cleaved caspase-1. The results of proteomics, central carbon metabolomics, western blot and immunohistochemical staining confirmed that JFG inhibited Glycolysis/Gluconeogenesis and Pentose phosphate pathway in the skin tissue of urticaria mice by activating the LKB1/AMPK/SIRT1 axis and then downregulating the protein expressions of Glut1, TORC2, p-CREB, PEPCK, HNF4α and G6Pase. CONCLUSION: The current study demonstrates that JFG is effective in treating OVA/aluminum hydroxide-induced skin lesions and inflammation in mice, and JFG exhibits the clinical benefits via modulating LKB1/AMPK/SIRT1 axis, which in turn inhibits Glycolysis/Gluconeogenesis and Pentose phosphate pathway.

Exploring the potential mechanism of Simiao Yongan decoction in the treatment of diabetic peripheral vascular disease based on network pharmacology and molecular docking technology.

The study aims to investigate the potential action targets and molecular mechanisms of Simiao Yongan decoction (SMYAD) in treating diabetic peripheral vascular disease (DPVD) by utilizing network pharmacology analysis and molecular docking technology. The components and targets of SMYAD were screened using the TCMSP database, while DPVD-related genes were obtained from the GeneCards, OMIM, and Disgenet databases. After intersecting the gene sets, a Protein-Protein Interaction (PPI) network was established, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. The practical chemical components and core targets identified were molecularly docked using AutoDock software. A total of 126 active compounds were screened from which 25 main components included quercetin, rutoside, hesperidin, naringin, and ß-sitosterol were determined to be the active components most associated with the core targets. A total of 224 common target genes were obtained. Among them, JUN, AKT1, MAPK3, TP53, STAT3, RELA, MAPK1, FOS, and others are the expected core targets of traditional Chinese medicine. The top-ranked GO enrichment analysis results included 727 biological processes (BP), 153 molecular functions (MF), and 102 cellular components (CC). KEGG pathway enrichment analysis involved mainly 178 signaling pathways, such as cancer signaling pathway, AGE-RAGE signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, endocrine resistance signaling pathway, cell aging signaling pathway, and so on. The molecular docking results demonstrate that the principal chemical components of SMYAD exhibit considerable potential for binding to the core targets. SMYAD has the potential to treat DPVD through various components, targets, and pathways. Its mechanism of action requires further experimental investigation.

Effectiveness of Chinese patent medicine in the treatment of influenza: A protocol for systematic review and meta-analysis.

BACKGROUND: Western medicine mainly uses antiviral drugs to treat influenza. However, anti-influenza virus drugs have been reported to have high levels of drug resistance and varying degrees of adverse reactions. In addition, Western medicine uses vaccination to prevent influenza, but vaccination cannot ensure complete prevention. Vaccines have a certain lag and cannot prevent the constantly mutating influenza virus. At present, there are still certain limitations in the prevention of influenza. In recent years, traditional Chinese medicine has been used more and more widely in the prevention and treatment of influenza and improvement of influenza-like symptoms, and related clinical efficacy control studies have reached a certain number. Therefore, the purpose of this study is to systematically evaluate the effectiveness of Chinese patent medicine in the treatment of influenza. METHODS: Computer search of PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP database, search for randomized controlled trials of Chinese patent medicines therapy on influenza, the search time limit is to build the database until October 2021. Two researchers screened the retrieved literature and collected relevant patient information and data. The final included literature was meta analyzed by Rev man5.4 software. RESULTS: The effectiveness and safety of Chinese patent medicines in the treatment of patients with influenza will be systematically evaluated. CONCLUSION: Systematic collection and analysis of clinical randomized controlled trials of Chinese patent medicines for the treatment of influenza, with a view to providing basic information for clinical decision-making and related research. REGISTRATION NUMBER: INPLASY2021100064 (https://inplasy.com/inplasy-2021- 10-0064/).

Antidepressant activity of ω-3 polyunsaturated fatty acids in ovariectomized rats: role of neuroinflammation and microglial polarization.

BACKGROUND: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. METHODS: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. RESULTS: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. CONCLUSION: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.

Discovery and structure-activity relationships of 6-(benzoylamino)benzoxaboroles as orally active anti-inflammatory agents.

Structure-activity relationships of 6-(benzoylamino)benzoxaborole analogs were investigated for the inhibition of TNF-α, IL-1ß, and IL-6 from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compound 1q showed potent activity against all three cytokines with IC50 values between 0.19 and 0.50µM, inhibited LPS-induced TNF-α and IL-6 elevation in mice and improved collagen-induced arthritis in mice. Compound 1q (AN4161) is considered to be a promising lead for novel anti-inflammatory agent with an excellent pharmacokinetic profile.

Benzoxaboroles: a new class of potential drugs for human African trypanosomiasis.

Human African trypanosomiasis, caused by the kinetoplastid parasite Trypanosoma brucei, affects thousands of people across sub-Saharan Africa, and is fatal if left untreated. Treatment options for this disease, particularly stage 2 disease, which occurs after parasites have infected brain tissue, are limited due to inadequate efficacy, toxicity and the complexity of treatment regimens. We have discovered and optimized a series of benzoxaborole-6-carboxamides to provide trypanocidal compounds that are orally active in murine models of human African trypanosomiasis. A key feature of this series is the presence of a boron atom in the heterocyclic core structure, which is essential to the observed trypanocidal activity. We also report the in vivo pharmacokinetic properties of lead compounds from the series and selection of SCYX-7158 as a preclinical candidate.

Immunosuppressive effects of demethylzeylasteral in a rat kidney transplantation model.

In this study, we examined the immunosuppressive activity of demethylzeylasteral (T-96), isolated from the traditional Chinese herbal medicine, Tripterygium wilfordii Hook f. Its immunosuppressive effect was investigated using mouse splenocytes in vitro, and in an in vivo rat kidney transplant model. T-96 inhibited mouse splenocyte proliferation in a dose dependent manner. In the rat kidney transplant study, rats were randomly divided into eight groups following kidney transplantation, and different doses of T-96 or cyclosporin A (CsA) were administered to each group. T-96 alone at doses of 10 or 20 mg/kg/day significantly prolonged the survival of kidney-transplanted rats, compared with transplanted but untreated control rats. A combination of T-96 and prednisone also significantly prolonged survival: 10 mg/kg/day T-96 with 10 mg/kg/day prednisone increased the survival time to 31.8+/-6.5 days. Moreover, the combination of T-96 and prednisone was also effective in suppressing rejection of rat transplanted kidneys. These results demonstrate the strong immunosuppressive activity of T-96 and suggest a possible clinical use for T-96 as an immunosuppressive agent in the fields of organ transplantation and autoimmune disorders.

Comparison of refluxing, ultrasonic- and microwave-assisted extraction of dihydromyricetin from Ampelopsis grossedentata.

Three techniques--refluxing extraction (RE), ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE)--for extraction of dihydromyricetin from Ampelopsis grossedentata, family Vitaceae, were evaluated. A 70% methanol-water solution was used as extraction solvent, and extracts obtained were analyzed by high-performance liquid chromatography (HPLC). Results showed that the MAE method was the most efficient in the shortest time, followed by RE and UAE. Maximum extraction efficiency of dihydromyricetin was obtained by using the MAE technique, which needs only 10 min, whereas UAE and RE require 40 and 300 min, respectively, to gain higher extraction efficiency of dihydromyricetin. The time needed for MAE was 30 times less than that needed for RE. Extracts obtained by using different methods were shown by HPLC analysis to possess similar chemical constituents, and extraction reproducibility was satisfactory for these techniques. Compared with UAE and RE, the MAE is a better alternative extraction technique for large-scale speedy extraction of dihydromyricetin from this plant.

[Chinese herbal medicine PC-SPES II induces the apoptosis of androgen-independent prostate carcinoma cell line PC-3].

OBJECTIVE: To study the action mechanism of a Chinese herbal mixture PC-SPES II inducing the apoptosis of androgen independent prostate adenocarcinoma cell line (PC-3). METHODS: The growth of PC-3 was shown by MTT. Immunofluorescence staining of acridine orange (AO) and flow cytometry were used to detect the apoptosis. The expressions of the apoptosis-related proteins were analyzed with their monoclonal or polyclonal antibodies after Western blotting. RESULTS: PC-SPES II not only inhibited the growth of PC-3 cells but also induced their death. The apoptosis of PC-3 cells treated with PC-SPES II was detected by immunofluorescence staining of AO and flow cytometry, which showed the apoptotic cells to be (29.8 +/- 5.6)%, but the untreated control cells (0.06 +/- 0.014)%, (P < 0.01). The expression of Bcl-2 and Bcl-xL, two antiapoptosis proteins, was decreased while Bax, a pro apoptosis protein, was elevated in the cells treated with PC-SPES II as compared with the untreated control (P < 0.01). Accordingly, the expression of the activated fragments of caspase-3 was also increased (P < 0.01). CONCLUSION: The Chinese herbal mixture PCSPES II can induce the apoptosis of PC-3. Its mechanism may lie in the up-regulation of Bax expression and down-regulation of Bcl-2 and Bcl-xL expressions, which induce the activated fragments of caspase-3 by mitochondria.

Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis.

A structure-activity relationship investigation for a more efficacious therapy to treat onychomycosis, a fungal infection of the toe and fingernails, led to the discovery of a boron-containing small molecule, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), which is currently in clinical trials for onychomycosis topical treatment.

[Effect of astrgaloside IV on the long-term consequences of renal ischemia-reperfusion injury in rat].

OBJECTIVE: To observe the effect of astrgaloside IV (Astr) on the long-term consequences of renal ischemia-reperfusion injury (IRI) in rat. METHODS: Fifty-four male Sprague-Dawley rats were randomized into 3 equal groups: IRI group, Astr group, and sham operation group. All rats underwent right nephrectomy and isolation of the left renal artery. The left renal arteries of the IRI group and Astr group were gripped by vascular clamp for 60 minutes and that of the sham operation group was only isolated without gripping. Two milliliters of Astr solution (0.1 g/L) was perfused into the stomach of the rats in the Astr group three days before and after the operation respectively. The rats in the IRI and sham operation groups were perfused with normal saline of the same volume. Four, twelve, and twenty-four weeks after the operation 24-hour urine specimens of the rats were collected to detect the urine protein. At each time point 6 rats from each group were anesthetized and blood was collected from the abdominal aorta to measure the level of serum creatinine (Cr), their left kidneys were taken out to undergo pathological examination and extraction of mRNA. Histochemistry was used to detect the expression of tumor growth factor (TGF)-beta1 protein in the renal tissues. RT-PCR was used to detect the expression of TGF-beta1 mRNA. Collagen staining and immunohistochemistry were used to measure the proportion of collagen positive material to the total area. RESULTS: The level of urine protein was increased progressively, those 12 and 24 weeks after the operation in the IRI group were significantly higher than those in the Astr and sham operation groups (all P < 0.05). The serum Cr 4 weeks after the operation was 36 micromol/L +/- 4 micromol/L, significantly higher than those in the Astr and sham operation groups (31 micromol/L +/- 8 micromol/L and 31 micromol/L +/- 5 micromol/L), and the serum Cr levels 4 weeks 12 and 24 weeks after the operation in the IRI group remained significantly higher than those in the Astr and sham operation groups (all P < 0.05). Collagen staining showed that the glomerular basement membrane, tunica adventitia vasorum, and adventitia of renal tubule were remarkably redder in the IRI than in the Astr and sham operation groups. The expression of TGF-beta1 protein was progressively increased since 12 weeks after the operation in the IRI group, significantly stronger in the Astr and sham operation groups. The expression of TGF-beta1 mRNA was progressively increased since 12 weeks after the operation in the IRI and Astr groups, significantly stronger than that in the sham operation group (P < 0.05). However, the expression of TGF-beta1 mRNA 24 weeks after the operation was significantly stronger in the IRI group than in the Astr group (P < 0.05). CONCLUSION: After renal IRI the probability of development of renal fibrosis increases. Astrgaloside IV markedly ameliorates renal injury by downregulating the TGF-beta1 expression.