Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Sheng-Xue-Xiao-Ban Capsule-induced ischemic colitis and pulmonary embolism in an idiopathic thrombocytopenic purpura patient: a rare case report.

Background: Sheng-Xue-Xiao-Ban Capsule (SXXBC), as a classic Chinese traditional medicine comprised of natural indigo, cortex moutan, forsythia, herba agrimoniae, and licorice, exhibits a heat-clearing and detoxicating function, hemostasis, and stasis dissipation, which is widely applied to treat idiopathic thrombocytopenic purpura (ITP). However, report on ischemic colitis and pulmonary embolism induced by SXXBC therapy is never disclosed. We report the case of an ITP patient who received SXXBC for ascending platelets that then induced ischemic colitis and pulmonary embolism. Case Description: A 74-year-old female patient was admitted in June 2021 due to "bleeding in stool for 1 day," she was then re-admitted in July 2021 due to "repeated bleeding in stool for 2 days". Abdominal computed tomography (CT), colonoscopy, and a pathological examination suggested ischemic colitis according to the American College of Gastroenterology (ACG) clinical guidelines. Pulmonary artery CT angiography suggested pulmonary embolism reflected by multiple filling defects, and the patient presented with shortness of breath. It was noted that the patient had started taken SXXBC for ascending platelets 2 months before the onset of hematochezia. After the diagnosis of hematochezia was made, the patient received phenethylamine and carbazochrome for hemostasis, mesalazine enteric-coated tablets for anti-inflammation, and SXXBC was stopped. The hematochezia then ceased, and the ischemic colitis was attenuated. Afterwards, low-molecular-weight heparin was administered, followed by a 3-week treatment of rivaroxaban anticoagulant, which was taken orally after discharge. The pulmonary embolism was then obviously ameliorated. After excluding other causes, the patient was diagnosed with SXXBC-induced ischemic colitis complicated by pulmonary embolism. After conducting research, we came to the view that natural indigo, which is the main component of SXXBC, contributed to the patient's illness. Conclusions: Ischemic colitis complicated with pulmonary embolism are rare; however, close attention such as regular abdominal CT test needs to be paid and preventive steps such as anti-coagulant treatment could to be taken (if symptoms occur) when treating patients with SXXBC.

HuangqiGuizhiWuwu Decoction Prevents Vascular Dysfunction in Diabetes via Inhibition of Endothelial Arginase 1.

Hyperglycemia induces vascular endothelial dysfunction, which contributes to the development of vascular complication of diabetes. A classic prescription of traditional medicine, HuangqiGuizhiWuwu Decoction (HGWWD) has been used for the treatment of various cardiovascular and cerebrovascular diseases, which all are related with vascular pathology. The present study investigated the effect of HGWWD treatment in streptozocin (STZ)-induced vascular dysfunction in mouse models. In vivo studies were performed using wild type mice as well as arginase 1 knockout specific in endothelial cells (EC-A1-/-) of control mice, diabetes mice and diabetes mice treated with HGWWD (60 g crude drugs/kg/d) for 2 weeks. For in vitro studies, aortic tissues were treated with mice serum containing HGWWD with or without adenoviral arginase 1 (Ad-A1) transduction in high glucose (HG) medium. We found that HGWWD treatment restored STZ-induced impaired mean velocity and pulsatility index of mouse left femoral arteries, aortic pulse wave velocity and vascular endothelial relaxation accompanied by elevated NO production in the aorta and plasma, as well as reduced endothelial arginase activity and aortic arginase 1 expression. The protective effect of HGWWD is reversed by an inhibitor of nitric oxide synthesis. Meanwhile, the preventive effect of serum containing HGWWD in endothelial vascular dysfunction is completely blocked by Ad-A1 transduction in HG incubated aortas. HGWWD treatment further improved endothelial vascular dysfunction in STZ induced EC-A1-/- mice. This study demonstrates that HGWWD improved STZ-induced vascular dysfunction through arginase 1 - NO signaling, specifically targeting endothelial arginase 1.

Anti-fatigue Effects of Active Ingredients from Traditional Chinese Medicine: A Review.

BACKGROUND: The application of traditional Chinese medicine (TCM) in the treatment of fatigue has long been practiced in clinical and showed significant effects. OBJECTIVE: This article summarizes the work done on the natural products from TCM that are reported to have effects of treating fatigue, in the past two decades. METHOD: Research status, sources, models, efficacy and mechanisms of active ingredients and their monomer in the treatment of fatigue are discussed. RESULTS: Pharmacological research shows that active ingredients of polysaccharide can significantly improve body's resistance through promoting glycogen synthesis, reducing sports metabolites and increasing hypoxia tolerance; Alkaloids have been proven to be effective in promoting the reserving of various glucogen substances, improving exercise endurance and speeding up the metabolism of body's urea nitrogen in mice; With the increase of glycosides amount, up goes the sport endurance, liver glycogen content and the ability of clear lactate index in mice, indicating that saponin has clear, dose-dependent anti-fatigue effect; Polyphenols have also functions of resisting fatigue, where they reduce free radicals accumulated and thus slow down the rapid declination of exercise capacity when doing sports; There are other active ingredients of TCM that have biological activities, like some proteins, anthraquinones, terpenes, unsaturated fatty acid monomer compounds; And research has found that tonic medicine can promote the elimination of fatigue and improve athletic ability. CONCLUSION: It is hoped that the data summarized in this review will be beneficial to the screening of new nature-derived drugs with the ability of relieving and improving fatigue.

Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice.

1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters. 2. In vitro uptake tests showed that jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 µM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1-1 µM (for OCT2 and OCT3) and 1-10 µM (for PMAT). 3. In mouse synaptosomes, jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant. 4. The antidepressant-like action of jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of jatrorrhizine (5, 10 and 20 mg/kg, i.p.) or venlafaxine (20 mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group. 5. The concentration of jatrorrhizine shows a dose-dependent increase in brain tissues. 6. Our study suggested that jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters.

Xiao-Shen-Formula, a Traditional Chinese Medicine, Improves Glomerular Hyper-Filtration in Diabetic Nephropathy via Inhibiting Arginase Activation and Heparanase Expression.

Hyperglycemia induces glomerular hyper-filtration, which contributes to the development of diabetic nephropathy (DN), a condition that remains a challenge for treatment. The present study investigated the effect of Xiao-Shen-Formula (XSF) used for treatment of renal injury in type 1 DN mice model induced by streptozotocin (STZ) and its underlying mechanism in cultured human glomerular endothelial cell (hGECs). Studies were performed using control, diabetic DN, DN treated with XSF groups (1 g/kg/d, LXSF or 3 g/kg/d, HXSF) for 6 weeks and hGECs were post-treated with mice serum containing HXSF (MS-HXSF) and arginase inhibitor (ABH, 100 µM) in high glucose medium. HXSF treatment restored STZ-induced renal hyper-filtration, glomerulosclerosis, renal microvascular remodeling and the increased levels of systemic reactive oxidative species and inflammatory cytokines, accompanied by preventing the decreased expression of glomerular heparin sulfate and the increased levels of cortical heparanase and argianse2 protein and arginase activity. In hGECs study, MS-HXSF ameliorated the enhancement in arginase activity, the protein/mRNA expression of heparanase, mRNA levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and permeability of hGECs monolayers as well as the depression of nitric oxide production. Besides all these protective effects, XSF blunted the mRNA expression of TNF-α in vivo and vitro studies as well, which was not changed by the post-treatment of ABH or HXSF plus ABH. This study demonstrated that the protective effect of XSF might be related with vascular prevention, anti-inflammation and anti-oxidation through intervening multi-targets including glomerular endothelial arginase-heparanase signaling pathway in DN model.

Treatment of Rosacea using acupuncture for improving the local skin microcirculation: A case report.

RATIONALE: Rosacea is an irritating disease that affects patients' health and life quality. The current treatments for rosacea have limited efficacy and are generally not satisfying most patients. This report presents a patient diagnosed with rosacea who was treated with acupuncture to a satisfactory effect. Laser Doppler was used to measure the local blood perfusion of the nose before, during, and after acupuncture treatment. The Dermatology Life Quality Index (DLQI) was used to measure the impact of rosacea on the quality of the patient's life. PATIENT CONCERNS: A 52-year-old woman had been diagnosed with rosacea 18 months before this study. She had tried medical treatments in other hospitals with metronidazole cream, antifungal drugs, and steroidal ointments, but the effect was poor and limited. DIAGNOSES: In this study, the diagnosis of rosacea (stage I, subtype Erythematotelangiectatic) was made by a dermatologist according to physical examination). INTERVENTIONS: The patient's treatment included a half-hour of acupuncture 3 times per week. OUTCOMES: The patient experienced significant improvements in the region around the nose after 3 sessions of acupuncture treatment within the first week and reported that there was no relapse for 6 months after acupuncture treatment. The perfusion of blood flow was redistributed during and after acupuncture treatment according to laser Doppler measurements. The patient's DLQI score substantially improved. The patient was generally satisfied with the acupuncture treatment. LESSONS: The results suggested that acupuncture might be an alternative therapy for facial localized rosacea. As well, acupuncture may be effective in treating rosacea through redistributing micro-circulation of blood at the localized area of effect. The overall costs of the rosacea treatment may be reduced, provided that this therapy is demonstrated to be effective in future controlled studies.

[Effect of shenfu injection on CYP450s of rat liver].

The paper is to report the study of the effect of Shenfu injection on the enzyme activity of liver CYP450 and its mRNA level of rat liver. Microsome of rat liver was prepared after intravenous administration of Shenfu injection for 7 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA expression of CYP1A2, CYP2B1/2, CYP2C11 and CYP3A1 in the liver was detected by RT-PCR. Shenfu injection obviously induced the enzyme activities of CYP2B and CYP2C. Meantime Shenfu injection decreased the enzyme activities of CYP1A2 and CYP3A. The mRNA levels of CYP2B and CYP2C were also induced in rats treated with Shenfu injection. But it obviously inhibited the mRNA level of CYP1A2 and CYP3A. Since the enzyme activity and mRNA level were obviously changed after administration, the potential effect of drug-drug interaction should be concerned.

[UPLC/Q-TOF-MS-based chemical profiling approach to evaluate the chemical constitution of Radix Aconiti Lateralis Preparata in the process of decoction].

OBJECTIVE: An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/Q-TOF-MS)-based chemical analytic technology was used to evaluate the chemical constitution of Radix Aconiti Lateralis Preparata in the process of decocting, so as to provide a scientific basis for processing Radix Aconiti Lateralis Preparata. METHODS: Radix Aconiti Lateralis Preparata samples with different decocting time were detected using UPLC/Q-TOF-MS to create a fingerprint spectrum. The data of tR-m/z pairs, ion intensities and sample codes were processed by partial least squared-discriminant analysis (PLS-DA) to holistically compare the difference among these samples. RESULTS: The contents of diester-diterpenoid alkaloid such as aconitine, mesaconitine and hypaconitine were higher between 2 to 10 min, while the contents of the lower toxic monoester-diterpenoid alkaloids such as benzoylaconine, benzoylmesaconine and benzoylhypaconine increased during the first 60 min, then their contents stabilized. CONCLUSION: Selecting the correct processing time for Radix Aconiti Lateralis Preparata according to clinical indications is essential for attenuating toxicity and increasing efficiency. Within 30 min is the best time for diester-diterpenoid alkaloids as the main pharmacodynamic material, and within 60 min is the best time for monoester-diterpenoid alkaloids as the pharmacodynamic material of Radix Aconiti Lateralis Preparata.

[Metabonomic study on siwu tang in radiation-induced blood deficient mice].

OBJECTIVE: To study the radiation-induced blood deficiency and the combination of prescription and syndrome of Siwu Tang using ultra performance liquid chromatography-quadrupoles-time of flight mass spectrometer (UPLC-ESI-Q-TOF-MS), in order to discover the changes in metabolic profiles of blood deficient mice induced by radiation, and clarify the relationship between blood deficient syndrome and the mechanism of Siwu Tang. METHOD: Thirty six C57 mice were randomly divided into three groups: the control group and the model model groups and the Siwu Tang group. The model was established by general irradiation with 3.5 Gy60 Coy ray. The animals were sacrificed on the 7th day after radiation and their blood, spleens and thymus were collected and detected using UPLC-ESI-Q-TOF/MS. MarkerLynx XS software was adopted to identify chromatographic peaks in the total ion chromatogram. Data was processed by making principal component analysis and analyzed by orthogonal partial least squares method among these groups, in order to rapidly identify marks through pattern recognition and analysis. RESULT: Compared with the control group, lysophosphatide, glucosiduronic acid, monoacylglycerol, erythronic acid, ceramide, aspartate phosphate ester, glyceryl phosphatide were obviously changed in the sera of the model group. Monoacylglycerol, ceramide, lysophosphatide, hydroxybutyric acid, palmitinic acid, 3-hydroxystearic acid, diethylarginine, neuraminic acid, phosphatidylserine were found in metabolites of their spleens. Methyladenosine, sitosterol, carnitine, phosphatidylinositol, phosphatidylethanolamine, diglyceride, dimethylarginine, ceramide, hydroxybutyric acid, cholesterol were found in thymus of the model group. CONCLUSION: Analysis on physiological functions of these biological markers show that radiation could induce the disorder of the metabolism of lipoid and carbohydrate and affect the synthesis of some amino acids, and Siwu Tang can reverse these effects.

[UPLC-TOF/MS based chemical profiling approach to evaluate toxicity-attenuated chemical composition in combination of ginseng and radix aconiti praeparata].

In the present study, an ultra performance liquid chromatography coupled with time-of-fight mass spectrometry (UPLC-TOF/MS) based chemical profiling approach was used to evaluate chemical constitution between co-decoction and mixed decoction of ginseng and Radix Aconiti Praeparata. Two different kinds of decoctions, namely co-decoction of ginseng and Radix Aconiti Praeparata: water extract of mixed two herbs, and mixed decoction of ginseng and Radix Aconiti Praeparata: mixed water extract of each individual herbs, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC-TOF/MS analysis. The datasets of t(R) m/z pairs, ion intensities and sample codes were processed with supervised partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between these two decoction samples. Significant difference between the two decoction samples was showed in the results of positive ion mode. The contents of hypaconitine and deoxyaconitine decreased, while that of benzoylmesaconine, benzoylhypaconine and dehydrated benzoylmesaconine increased in the samples of co-decoction of ginseng and Radix Aconiti Praeparata. The content of diester-diterpenoid alkaloids decreased, while that of monoester-diterpenoid alkaloids increased, which is probably the basis of toxicity-attenuated action when combined ginseng with Radix Aconiti Praeparata.