Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification.

BACKGROUND: Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. METHOD: Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. RESULT: The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. CONCLUSION: Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.

Key circRNAs, lncRNAs, and mRNAs of ShenQi Compound in Protecting Vascular Endothelial Cells From High Glucose Identified by Whole Transcriptome Sequencing.

ABSTRACT: Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.

Scutellarein alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis by chelating iron and interacting with arachidonate 15-lipoxygenase.

Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, is involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Therefore, ferroptosis inhibition represents an attractive strategy for COPD therapy. Herein, we identified natural flavonoid scutellarein as a potent ferroptosis inhibitor for the first time, and characterized its underlying mechanisms for inhibition of ferroptosis and COPD. In vitro, the anti-ferroptotic activity of scutellarein was investigated through CCK8, real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, flow cytometry, and transmission electron microscope (TEM). In vivo, COPD was induced by lipopolysaccharide (LPS)/cigarette smoke (CS) and assessed by changes in histopathological, inflammatory, and ferroptotic markers. The mechanisms were investigated by RNA-sequencing (RNA-seq), electrospray ionization mass spectra (ESI-MS), local surface plasmon resonance (LSPR), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular dynamics. Our results showed that scutellarein significantly inhibited Ras-selective lethal small molecule (RSL)-3-induced ferroptosis and mitochondria injury in BEAS-2B cells, and ameliorated LPS/CS-induced COPD in mice. Furthermore, scutellarein also repressed RSL-3- or LPS/CS-induced lipid peroxidation, GPX4 down-regulation, and overactivation of Nrf2/HO-1 and JNK/p38 pathways. Mechanistically, scutellarein inhibited RSL-3- or LPS/CS-induced Fe2+ elevation through directly chelating Fe2+ . Moreover, scutellarein bound to the lipid peroxidizing enzyme arachidonate 15-lipoxygenase (ALOX15), which resulted in an unstable state of the catalysis-related Fe2+ chelating cluster. Additionally, ALOX15 overexpression partially abolished scutellarein-mediated anti-ferroptotic activity. Our findings revealed that scutellarein alleviated COPD by inhibiting ferroptosis via directly chelating Fe2+ and interacting with ALOX15, and also highlighted scutellarein as a candidate for the treatment of COPD and other ferroptosis-related diseases.

Renoprotective Effects of Tanshinone IIA: A Literature Review.

The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid-base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by year worldwide, and they have become a serious public health problem. In recent years, natural products derived from fungi, plants and animals have become an important alternative source of treatment for kidney diseases because of their multiple pathways, multiple targets, safety, low toxicity and few side effects. Tanshinone IIA (Tan IIA) is a lipid-soluble diterpene quinone isolated from the Chinese herb Salvia miltiorrhiza, considered as a common drug for the treatment of cardiovascular diseases. As researchers around the world continue to explore its unknown biological activities, it has also been found to have a wide range of biological effects, such as anti-cancer, anti-oxidative stress, anti-inflammatory, anti-fibrotic, and hepatoprotective effects, among others. In recent years, many studies have elaborated on its renoprotective effects in various renal diseases, including diabetic nephropathy (DN), renal fibrosis (RF), uric acid nephropathy (UAN), renal cell carcinoma (RCC) and drug-induced kidney injury caused by cisplatin, vancomycin and acetaminophen (APAP). These effects imply that Tan IIA may be a promising drug to use against renal diseases. This article provides a comprehensive review of the pharmacological mechanisms of Tan IIA in the treatment of various renal diseases, and it provides some references for further research and clinical application of Tan IIA in renal diseases.

[Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions"].

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Direct Analysis of Soil Composition for Source Apportionment by Laser Ablation Single-Particle Aerosol Mass Spectrometry.

Soil has always been the most complex biomaterial on the planet. The rapid determination of the components in the soil and their original source is a prerequisite for soil quality, environmental, and human health risk assessments. In this study, the chemical compositions and source apportionment of surface soil samples collected from five sites in Shanghai, China, were successfully investigated using a laboratory-developed laser ablation single-particle aerosol mass spectrometry (LA-SPAMS) instrument combined with an adaptive resonance theory-based neural network algorithm (ART-2a) data-processing method for the first time. In total, more than 35,000 particles, ranging from 200 to 2000 nm, were sized, and around 15-20% of the particles were chemically analyzed by LA-SPAMS to generate both positive and negative mass spectra. The results show that there are significant differences in particle size distribution among the five samples, with peaks of various sizes and different profiles, while all five soil samples contain crustal elements, heavy metals, organic and inorganic components, and so forth. The chemical composition of each sample varied considerably, so different classes of SPAMS particle classes were identified, which were later grouped into seven general categories: EC-rich (containing elemental carbon), secondary components, organic nitrogen, crust, HM (containing heavy metal), PAH (containing polycyclic aromatic hydrocarbons), and NaK-rich particles, based on the dominant marked ions. The composition analysis and source apportionment showed that soil components in different areas have been affected by the local environment, such as local industrial emissions and automobile exhaust, which are usually characterized by varying degrees of mixing between the crust and environmental aerosols. In combination with the ART-2a method, LA-SPAMS enables rapid and direct analysis of soil samples based on real-time single-particle measurements, which will help in understanding the distribution, transport, and fate of the soil components, thus providing new insights into soil-quality assessment. Moreover, the established LA-SPAMS can also be practically applied to other daily inspection tasks, such as rocks, minerals, metals, ceramics, polymers, and other solid materials for ingredient analysis and quality evaluation.

Add-on effect of Qiming granule, a Chinese patent medicine, in treating diabetic macular edema: A systematic review and meta-analysis.

This study aims to evaluate the efficacy and safety of Qiming granule (QG) on diabetic macular edema (DME). PubMed, Embase, the Cochrane Library, CNKI, Wanfang, qvip and China Biology Medicine Disc were searched. Randomized controlled trials (RCTs) about participants with a diagnosis of DME were included. Risk of bias assessment was conducted by Cochrane risk-of-bias tool for RCT. Random-effects model was implemented to pool results. Among 16 included studies, QG combined with conventional treatment was administered 13.5 g daily for a period ranging from 2 to 6 months. Results showed combination therapy was more effective than conventional treatment alone in central macular thickness (weighted mean difference (WMD) = -29.43, 95% confidence interval (CI) (-39.56 to -19.29), p = .0001), optimum corrected vision (pooled standardized mean difference (SMD) = -0.962, 95%CI (-1.35 to -0.57), p = .0001) and overall effective rate (RR = 1.25, 95%CI = [1.13 to 1.35], p < .0001). Only three studies reported adverse effects. The quality of evidence is low. Due to a lack of placebo control, the net efficacy of QG is still uncertain. More high-quality RCTs are needed to confirm the efficacy and safety of QG in DME.

[Dao-di herbs pharmacology and new ideas of Dao-di herbs standard construction].

Guided by the basic theory of traditional Chinese medicine and using modern scientific methods, Dao-di herbs pharmacology studies the nature, performance, interaction with the body and its clinical application.It is a bridge between the basic research and clinical application of Dao-di herbs. It can objectively describe the law of efficacy of Dao-di herbs, scientifically explain the mechanism of efficacy of Dao-di herbs, explore and establish the standards and methods of Dao-di herbs based on biological effect and clinical efficacy, and provide scientific basis for the special properties, pharmacology and clinical value of Dao-di herbs.Furthermore, we put forward a new idea of building the standard of Dao-di herbs based on the curative effect rather than the origin.The Dao-di herbs standard should come from the systematic research of traditional Dao-di herbs producing areas and form a new characteristic system, through the extraction of environmental, genetic, character, chemical, pharmacological and other characteristics.This standard originates from the tradition, but it is higher than the tradition. It may not have the origin meaning of strict administrative division, but it can better reflect the pharmacological characteristics and excellent clinical value of Dao-di herbs.

[Protection and mechanism of shenqi compound for diabetic angiopathy model rats].

OBJECTIVE: To investigate the protective effect and mechanism of Shenqi Compound on diabetic angiopathy modeled rats. METHODS: Totally 18 SD rats were randomized into 3 groups, i.e., the normal control group, the diabetic mellitus (DM) group, and Shenqi Compound group, 6 in each group. The DM rat model was established by feeding high-fat diet (to induce hyperlipidemia) +intraperitoneal injection of small dose streptozotocin (STZ). Shenqi Compound was given to rats in the Shenqi Compound group at the daily dose of 2 g/kg. Equal volume of normal saline was given to rats in the model group and the normal control group by gastrogavage. All treatment was lasted for 12 weeks. Then 2-D and ultrasonic integrated backscatter technique were used to evaluate structural and functional changes of abdominal aorta in the progression of diabetic macroangiopathy. The fibrosis degree of the aorta vessel and myocardium capillaries were observed by using HE and Masson trichrome staining. The tension of the aortic vascular ring was determined. The transforming growth factor beta (TGF-beta) mRNA expression was detected by real time PCR (RT-PCR). The protein expression of TGF-beta, collagen I, collagen III, connective tissue growth factor (CTGF), and phosphorylation P38 MAPK were detected by Western blot. RESULTS: Compared with the normal control group, abdominal aortic systolic inner diameter, diastolic inner diameter, Peterson elastic modulus, stiffness index, and backscatter integral significantly increased; the rangeability of integral backscatter and the extension coefficient of cross section significantly decreased in the DM group (all P < 0.05). After 12 weeks aforesaid indices were obviously improved in the Shenqi Compound group (P < 0.05). Results of HE and Masson staining showed that the fibrosis degree of the aorta vessel and myocardium capillaries was obviously alleviated in rats of the Shenqi Compound group (P < 0.05). Results of the aortic vascular ring tension showed that acetylcholine induced vasodilatation and maximum diastolic percent were obviously elevated in the Shenqi Compound group (P < 0.05). Compared with the normal control group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all significantly increased in the DM group (P < 0.05). Compared with the DM group, the mRNA expression of TGF-beta, and the protein expression of TGF-beta, collagen I, and collagen III, and phosphorylation of P38 MAPK all decreased (P < 0.05). CONCLUSIONS: Shenqi Compound could effectively improve the arterial function in diabetic marcoangiopathy and microvascular dysfunction. The mechanism might be due to the down-regulating the expression of TGF-beta, and further suppressing the phosphorylation of P38 MAPK, reducing the synthesis of collagen I and collagen III, therefore, ameliorating arterial and myocardial interstitial fibrosis.

Inhibited hypoxia-inducible factor by intraoperative hyperglycemia increased postoperative delirium of aged patients: A review.

The underlying mechanism of postoperative delirium (POD) in elderly people remains unclear. Perioperative hyperglycemia (POHG) is an independent risk indicator for POD, particularly in the elderly. Under cerebral desaturation (hypoxia) during general anesthesia, hypoxia-inducible factor (HIF) is neuroprotective during cerebral hypoxia via diverse pathways, like glucose metabolism and angiogenesis. Hyperglycemia can repress HIF expression and activity. On the other hand, POHG occurred among patients undergoing surgery. For surgical stress, hypothalamic-pituitary-adrenal activation and sympathoadrenal activation may increase endogenous glucose production via gluconeogenesis and glycogenolysis. Thus, under the setting of cerebral hypoxia during general anesthesia, we speculate that POHG prevents HIF-1α levels and function in the brain of aged patients, thus exacerbating the hypoxic response of HIF-1 and potentially contributing to POD. This paper sketches the underlying mechanisms of HIF in POD in elderly patients and offers novel insights into targets for preventing or treating POD in the same way as POHG.

Investigation of the hypoglycemic mechanism of the ShenQi compound formula through metabonomics and 16S rRNA sequencing.

Introduction: Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by in vitro studies. However, the hypoglycemic effect and underlying mechanisms of Shenqi Compound (SQ), a traditional Chinese herbal formula, remain elusive. This study aimed to elucidate the hypoglycemic effects of SQ and explore its mechanisms of action, focusing on intestinal flora and metabolomics. Methods: A Type 2 diabetes mellitus (T2DM) rat model was established through a high-fat diet, followed by variable glucose and insulin injections to mimic the fluctuating glycemic conditions seen in diabetes. Results: An eight-week regimen of SQ significantly mitigated hyperglycemia, inflammation, and insulin resistance in these rats. Notably, SQ beneficially modulated the gut microbiota by increasing populations of beneficial bacteria, such as Lachnospiraceae_NK4A136_group and Akkermansia, while reducing and inhibiting harmful strains such as Ruminococcus and Phascolarctobacterium. Metabolomics analyses revealed that SQ intervention corrected disturbances in Testosterone enanthate and Glycerophospholipid metabolism. Discussion: Our findings highlight the hypoglycemic potential of SQ and its mechanisms via modulation of the gut microbiota and metabolic pathways, offering a theoretical foundation for the use of herbal medicine in diabetes management.

A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches.

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

Stereoscopic imaging of volatile organic compounds distribution in the region and tracing emission sources of volatile organic compounds using a novel movable single-photon ionization time-of-flight mass spectrometer.

This paper presents a newly developed high-performance mobile single-photon ionization time-of-flight mass spectrometry (M-SPI-TOFMS) system for on-line analysis and stereoscopic monitoring of complex gas mixtures. The system is designed for stereoscopic imaging to map the distribution of volatile organic compounds (VOCs) and trace their emission sources in urban areas and industrial parks. It mainly consists of a SPI-TOFMS instrument, a customized commercial vehicle, a meteorological five-parameter monitor with GPS, a high-power generator, and an uninterruptible power supply. The SPI technique, using a 118 nm VUV lamp, can ionize compounds with an ionization potential below 10.78 eV. Mass spectra obtained using this technique show the profiles of various VOCs and some inorganic compounds. The VOCs composition information and mobile location data are simultaneously sent to the GIS software. In GIS software, this data is used for real-time stereoscopic imaging of VOC distribution and precise tracking of VOC movement. The system can achieve a spatial data resolution of 0.69 mm at 25 km/h due to the microsecond detection speed of the M-SPI-TOFMS instrument. The laboratory test provides a rapid overview characterization of benzene, toluene, and xylene. The M-SPI-TOFMS has limits of detection and mass resolution of 33.7 pptv and 1060, respectively. Several field applications were carried out using M-SPI-TOFMS at various locations to identify VOC sources near different factories. The M-SPI-TOFMS system has a navigation monitoring speed of 25 km/h with a time resolution of 1 s. The widespread use of this system will provide accurate data to support environmental management departments in formulating VOCs pollution control policies and improving control efficiency.

Boosting the sensitivity of single photon ionization time-of-flight mass spectrometry using a segmented focus quadrupole-ion guide.

Single photon ionization time-of-flight mass spectrometry (SPI-TOF-MS) is a powerful analytical technique for real-time detection of trace VOCs. However, efficient ion transmission within the ionization chamber has always been a challenging issue in SPI-TOF-MS. In this study, a novel ion guide termed the Segmented Focus Quadrupole Ion Guide (SFQ-IG) was introduced for SPI-TOF-MS. The SFQ-IG device consists of 12 printed circuit boards (PCB), each containing four quarter-ring electrodes with inner diameters progressively decreasing from 26 to 4 mm. The simulation results demonstrated that SFQ-IG exhibited superior ion transmission efficiency than both ion funnel (IF) field and direct current-only (DC-only) field. By integrating into a SPI-TOF-MS, this ion guide was optimized in terms of the ionization source pressure, direct current gradient, and radio frequency amplitude. Further comparative experiments demonstrated that the SPI-TOF-MS with the SFQ-IG exhibited higher sensitivity than both the IF field (1.3-7.4 times) and DC-only field (3.5-8.8 times) for the test VOCs. The improvements in limit of detection (LOD) with the SFQ-IG ranged from 1.6 to 5.3 times compared to the DC-only field for the test VOCs. Fabricated using PCB technology, the SFQ-IG is characterized by its cost-effectiveness, compact size, and high transmission efficiency, facilitating its integration into other mass spectrometers.

Mitochondrial proteins as therapeutic targets in diabetic ketoacidosis: evidence from Mendelian randomization analysis.

Introduction: Diabetic ketoacidosis (DKA) is a severe and potentially fatal acute complication in diabetic patients, commonly occurring in type 1 diabetes (T1D) but also seen in type 2 diabetes (T2D). The pathogenesis of DKA involves complex physiological processes that are not fully understood, especially the role of mitochondria. Mitochondria, known as the powerhouse of cells, plays a crucial role in oxidative phosphorylation and ATP production, which is vital in various metabolic diseases, including diabetes. However, the exact causal relationship between mitochondrial dysfunction and DKA remains unclear. Methods: This study employed Mendelian randomization (MR) analysis and protein-protein interaction (PPI) networks to systematically explore the causal relationships between mitochondrial DNA copy number (mtDNA-CN) and specific mitochondrial proteins with DKA. We used bidirectional MR analysis and genome-wide association study (GWAS) data from openGWAS database to investigate the causal effects of mtDNA-CN and 64 mitochondrial-related proteins on DKA and its subtypes (T1DKA, T2DKA, unspecified-DKA). Results: The study revealed that increased mtDNA-CN significantly reduces the risk of DKA, whereas the effect of DKA on mtDNA-CN was not significant. Mitochondrial-related proteins such as MRPL32, MRPL33, COX5B, DNAJC19, and NDUFB8 showed a negative causal relationship with DKA, indicating their potential protective roles. Conversely, ATP5F1B and COX4I2 have a positive causal relationship with DKA, indicating that excessive ATP production in diabetic patients may be detrimental to health and increase the risk of severe complications such as DKA. Discussion: The results emphasize the necessity of protecting mitochondrial function in order to reduce the risk of DKA. The study offers novel perspectives on the molecular pathways involved in DKA, emphasizing the critical functions of mt-DNA and distinct proteins. These evidences not only enhance our comprehension of the implications of mitochondrial dysfunction in diabetes-related complications but also identify potential therapeutic targets for individualized treatment approaches, thereby making a substantial contribution to clinical care and public health initiatives.

Cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles inhibits breast cancer-bone metastasis by targeting JAK-STAT signaling pathways.

Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.

The research progress of crosstalk mechanism of autophagy and apoptosis in diabetic vascular endothelial injury.

In recent years, the widespread prevalence of diabetes has become a major killer that threatens the health of people worldwide. Of particular concern is hyperglycemia-induced vascular endothelial injury, which is one of the factors that aggravate diabetic vascular disease. During the process of diabetic vascular endothelial injury, apoptosis is an important pathological manifestation and autophagy is a key regulatory mechanism. Autophagy and apoptosis interact with each other. Hence, the crosstalk mechanism between the two processes is an important means of regulating diabetic vascular endothelial injury. This article reviews the research progress in apoptosis in the context of diabetic vascular endothelial injury and discusses the crosstalk mechanism of autophagy and apoptosis and its role in this injury. The purpose is to guide the prevention and treatment of diabetic vascular endothelial injury in the future.

Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets.

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA have many side effects and limitations, are unable to prevent recurrent GA attacks and tophus formation, and overall efficacy is unsatisfactory. Therefore, we need to advance research on the microscopic mechanism of GA and seek safer and more effective drugs through relevant targets to block the GA disease process. Current research shows that the pathogenesis of GA is closely related to NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, and Ferroptosis. However, after synthesizing and sorting out the above mechanisms, it is found that the presence of ROS is throughout almost the entire spectrum of micro-mechanisms of the gout disease process, which combines multiple immune responses to form a large network diagram of complex and tight connections involved in the GA disease process. Current studies have shown that inflammation, oxidative stress, cell necrosis, and pathological signs of GA in GA joint tissues can be effectively suppressed by modulating ROS network-related targets. In this article, on the one hand, we investigated the generative mechanism of ROS network generation and its association with GA. On the other hand, we explored the potential of related targets for the treatment of gout and the prevention of tophus formation, which can provide effective reference ideas for the development of highly effective drugs for the treatment of GA.

Combination of traditional Chinese medicine and standard biomedical treatment for rosacea: a systematic review and a meta-analysis.

Background: A combination of standard biomedical treatment and traditional Chinese medicine (TCM) has been suggested as a therapeutic approach for rosacea that may significantly lower the recurrence rate and clinical symptom scores. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of this combination treatment on clinical symptom and TCM syndrome scores, as well as on the scores of the Dermatology Life Quality Index (DLQI), erythema index (EI), and interleukin 37 (IL-37) levels in patients with rosacea. Methods: The PROSPERO registration number for the study is CRD42023472737. We systematically searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure Wanfang Database, China Biomedical Medicine database (CBM), and the VIP information resource integration service platform (cqvip) databases for RCTs (published from the beginning to September 2023, regardless of the language used) that compared the traditional Chinese medicine and standard biomedical treatment combination treatment to conventional anti-rosacea treatments. Our primary outcomes comprised the clinical symptom and TCM syndrome scores, and the scores of Dermatology Life Quality Index, erythema index, and IL-37 levels. We used a random-effects model to evaluate the pooled data. Results: We identified 260 studies. Of these, 13 eligible studies were employed for analysis (N = 1,348 participants). Compared with other anti-rosacea treatments, the TCM and standard biomedical treatment combination treatment yielded an improved mean reduction in the clinical symptom score -2.24% [95% CI (-3.02 to -1.46), p < 0.00001], TCM syndrome score -4.42 [95% CI (-5.33 to -3.50), p < 0.00001], and the score of DLQI of -2.55 [95% CI (-3.73 to -1.36), p < 0.00001], EI of -151.97 [95% CI (-276.59 to -27.36), p < 0.00001], and IL-37 level -4.23 [95% CI (-4.95 to -3.51), p = 0.854], as well as in the overall effective rate risk ratio (RR) = 1.25 [95%CI (1.18, 1.32), p = 0.994] and the recurrence rate = 0.27 [95%CI (0.15, 0.46), p = 0.297]. Conclusion: The TCM and standard biomedical treatment combination treatment can provide a better outcome, including a reduction in the TCM syndrome and clinical symptom scores, and in the scores of DLQI, EI, and IL-37. Hence, this combination is a viable and more effective therapeutic approach for rosacea. However, these results should be considered cautiously because of uncertain evidence and the low quality of the study reports considered in this meta-analysis. Systematic Review Registration: website, identifier CRD42023472737.

The potential of astragalus polysaccharide for treating diabetes and its action mechanism.

Type 2 diabetes presents a significant global health burden and is frequently linked to serious clinical complications, including diabetic cardiomyopathy, nephropathy, and retinopathy. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, exhibits various biochemical and physiological effects. In recent years, a growing number of researchers have investigated the role of APS in glucose control and the treatment of diabetes and its complications in various diabetes models, positioning APS as a promising candidate for diabetes therapy. This review surveys the literature on APS from several databases over the past 20 years, detailing its mechanisms of action in preventing and treating diabetes mellitus. The findings indicate that APS can address diabetes by enhancing insulin resistance, modulating the immune system, protecting islet cells, and improving the intestinal microbiota. APS demonstrates positive pharmacological value and clinical potential in managing diabetic complications, including diabetic retinopathy, nephropathy, cardiomyopathy, cognitive dysfunction, wound healing, and more. However, further research is necessary to explore APS's bioavailability, optimal dosage, and additional clinical evidence.