The mechanism and promising therapeutic strategy of diabetic cardiomyopathy dysfunctions: Focus on pyroptosis.

Diabetes is a major risk factor for cardiovascular diseases, and myocardial damage caused by hyperglycemia is the main cause of heart failure. However, there is still a lack of systematic understanding of myocardial damage caused by diabetes. At present, we believe that the cellular inflammatory damage caused by hyperglycemia is one of the causes of diabetic cardiomyopathy. Pyroptosis, as a proinflammatory form of cell death, is closely related to the occurrence and development of diabetic cardiomyopathy. Therefore, this paper focuses on the important role of inflammation in the occurrence and development of diabetic cardiomyopathy. From the perspective of pyroptosis, we summarize the pyroptosis of different types of cells in diabetic cardiomyopathy and its related signaling pathways. It also summarizes the treatment of diabetic cardiomyopathy, hoping to provide methods for the prevention and treatment of diabetic cardiomyopathy by inhibiting pyroptosis.

Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

[Traditional Chinese medicines target neutrophil extracellular traps to treat diseases: a review].

Neutrophil extracellular traps(NETs) are fibrous networks formed by neutrophils after a procedure called NETosis, with the function of capturing and killing pathogens. NETs are widely involved in the pathological processes of major diseases such as immune system diseases, respiratory diseases, metabolic diseases, cancers, and reperfusion injury. Therefore, regulating NETs has become one of the important ways to prevent and treat the above diseases. As an excellent traditional culture in China, traditional Chinese medicine has made outstanding contributions to the treatment of diseases. In recent years, studies have discovered that a variety of active components in traditional Chinese medicines, Chinese medicine compound prescriptions, and single traditional Chinese medicines can alleviate the symptoms by regulating NETs in the pathological process of major diseases. This article reviews the research progress in the regulation of NETs by the active components of traditional Chinese medicines, Chinese medicine compound prescriptions, and single traditional Chinese medicines in the last five years, aiming to serve as a reference for related research.

Gut microbiota influence frailty syndrome in older adults: mechanisms and therapeutic strategies.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

Citropten alleviates acute and recurrent colitis via blockage of NF-κB and JAK/STAT3 pathways.

Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD.

The role of mitochondria in myocardial damage caused by energy metabolism disorders: From mechanisms to therapeutics.

Myocardial damage is the most serious pathological consequence of cardiovascular diseases and an important reason for their high mortality. In recent years, because of the high prevalence of systemic energy metabolism disorders (e.g., obesity, diabetes mellitus, and metabolic syndrome), complications of myocardial damage caused by these disorders have attracted widespread attention. Energy metabolism disorders are independent of traditional injury-related risk factors, such as ischemia, hypoxia, trauma, and infection. An imbalance of myocardial metabolic flexibility and myocardial energy depletion are usually the initial changes of myocardial injury caused by energy metabolism disorders, and abnormal morphology and functional destruction of the mitochondria are their important features. Specifically, mitochondria are the centers of energy metabolism, and recent evidence has shown that decreased mitochondrial function, caused by an imbalance in mitochondrial quality control, may play a key role in myocardial injury caused by energy metabolism disorders. Under chronic energy stress, mitochondria undergo pathological fission, while mitophagy, mitochondrial fusion, and biogenesis are inhibited, and mitochondrial protein balance and transfer are disturbed, resulting in the accumulation of nonfunctional and damaged mitochondria. Consequently, damaged mitochondria lead to myocardial energy depletion and the accumulation of large amounts of reactive oxygen species, further aggravating the imbalance in mitochondrial quality control and forming a vicious cycle. In addition, impaired mitochondria coordinate calcium homeostasis imbalance, and epigenetic alterations participate in the pathogenesis of myocardial damage. These pathological changes induce rapid progression of myocardial damage, eventually leading to heart failure or sudden cardiac death. To intervene more specifically in the myocardial damage caused by metabolic disorders, we need to understand the specific role of mitochondria in this context in detail. Accordingly, promising therapeutic strategies have been proposed. We also summarize the existing therapeutic strategies to provide a reference for clinical treatment and developing new therapies.

Roxarsone inhibits hepatic stellate cell activation and ameliorates liver fibrosis by blocking TGF-ß1/Smad signaling pathway.

Hepatic fibrosis is a pathological change caused by chronic liver injury and self-repair, and it is the inevitable stage of the development of chronic liver disease to cirrhosis or even liver cancer. Activation of hepatic stellate cells (HSCs) is a core event in the development of liver fibrosis and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Roxarsone, an organoarsenic additive, with antibiotic effect, growth promotion and improving feed efficiency, is widely used in livestock and animal production. The purpose of this study was to evaluate the therapeutic effect of Roxarsone on liver fibrosis and explore the possible mechanism. We found that Roxarsone could inhibit transforming growth factor-ß1 (TGF-ß1) induced the activation of HSCs and weaken the migration ability. Moreover, Roxarsone administration significantly ameliorated CCl4-induced liver fibrosis in mice with improvement of liver function and decreases of deposition of extracellular matrix (ECM). Mechanism investigations revealed that Roxarsone specifically inhibited the activation of TGF-ß1/Smad signaling pathway, but had no effect on MAPK and PI3K/AKT pathways. These results suggest that Roxarsone has a protective effect on liver fibrosis which provides a new candidate for the treatment of liver fibrosis.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms.

Qishen Yiqi Dripping Pills (QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside IV, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3.

Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti-tumor, anti-oxidant, anti-viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM-induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING-finger containing protein-1 (MuRF1) and muscle atrophy Fbox protein (Atrogin-1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.

Polydatin alleviates DSS- and TNBS-induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

Cryptotanshinone ameliorates dextran sulfate sodium-induced murine acute and chronic ulcerative colitis via suppressing STAT3 activation and Th17 cell differentiation.

Ulcerative colitis (UC) is a chronically relapsing inflammatory disease in the intestinal tract. Current unsatisfactory treatments prompt people to seek for alternative therapies and drug candidates. Cryptotanshinone (CTS), a diterpene quinoneextractedfromthe roots ofSalviamiltiorrhiza, has recently been shown to inhibit acute colitis by reducing pro-inflammatory mediators. However, whether CTS can protect against chronic UC and its effect on T lymphocytes remain unknown. In this study, CTS (20, 60 mg/kg) showed potent inhibitory activity against dextran sulfate sodium (DSS)-induced acute UC, as determined by weight loss, disease activity, colon length and histology. Similarly, in a model of DSS-induced chronic colitis, the administration of CTS prevented the disease progression with longer colon length, lower histological scores, and less expression of fibrosis-related collagen and α-smooth muscle actin in the colon. CTS also reduced the proportion of CD4+IL-17A+ Th17 cells in spleen and mesenteric lymph nodes of mice with acute or chronic colitis. However, CTS at 20 mg/kg had no effect on regulatory T cells (Tregs). In addition, CTS reduced the phosphorylation of signal transduction and transcription activator 3 (STAT3) in DSS-treated colon tissue. Further study showed that CTS concentration-dependently suppressed the differentiation of naïve CD4+ T cells into Th17 cells. CTS could not inhibit the activation and proliferation of T lymphocytes or attenuate the secretion of cytokines including IL-10, IL-2, IL-6 and IFN-γ, but could inhibit the production of IL-17A and TNF-α in Con A-stimulated splenocytes. CTS suppressed IL-6-induced phosphorylation and nuclear translocation of STAT3. In conclusion, our study demonstrated that CTS alleviated acute and chronic UC by suppressing STAT3 activation and Th17 cell differentiation, suggesting that it may be a promising candidate drug for the treatment of UC.

[Effect of panlong needling at Jiaji (EX-B 2) on motor dysfunction in patients with Parkinson's disease of liver and kidney deficiency: a randomized controlled trial].

OBJECTIVE: To compare the curative effect of panlong needling at Jiaji (EX-B 2) combined with western medication and western medication alone on motor dysfunction in patients with Parkinson's disease (PD) of liver and kidney deficiency. METHODS: A total of 98 patients with PD were randomly divided into an acupuncture and medication group (49 cases, 1 case dropped off) and a western medication group (49 cases,1 case was removed). The patients in the western medication group were given oral of levodopa and benserazide hydrochloride tablets, 125 mg each time, three times a day in the 1st week, and the dose was increased according to the needs of the patients' condition from the 2nd week until 250 mg each time, three times a day, for 16 consecutive weeks. On the basis of the same western medication treatment as the western medication group, panlong needling was applied at Jiaji (EX-B 2) from C2 to L5 in the acupuncture and medication group, once a day, 20 times as a course of treatment, for 4 consecutive courses. The scores of unified Parkinson's disease rating scale (UPDRS-Ⅲ, UPDRS-Ⅳ), TCM symptoms score, and 39-item Parkinson's disease questionnaire (PDQ-39) score were evaluated before treatment, after treatment and during follow-up of 1 month after treatment, respectively. The safety of the two groups was compared. RESULTS: After treatment and during follow-up, except the PDQ-39 score of the western medication group, the scores of UPDRS-Ⅲ, UPDRS-Ⅳ, TCM syndrome and PDQ-39 were lower than those before treatment in the two groups (P<0.05), and the scores of above indexes in the acupuncture and medication group were lower than those of the western medication group (P<0.05). The total incidence of adverse reactions in the acupuncture and medication group was 10.4% (5/48), which was lower than 29.2% (14/48) in the western medication group (P<0.05). CONCLUSION: Panlong needling at Jiaji (EX-B 2) combined with western medication could significantly improve the motor dysfunction and clinical symptoms, improve the quality of life and has high safety, and the efficacy is superior to western medication alone.

A novel process for food waste recycling: A hydrophobic liquid mulching film preparation.

Appropriate and effective recycling of food waste (FW) has become increasingly significant with the promotion of garbage classification in China. In this study, a novel and green process was developed to recycle FW to prepare a biodegradable composite liquid mulching film (LMF) through crosslinking with sodium alginate (SA). The solid phase of FW was obtained as the raw material after hydrothermal pretreatment to remove pathogens and salts, and to improve the reactivity of active components at a moderate temperature. The prepared LMF had a hydrophobic surface and compact structure due to the lipid in FW and the acetalization reaction and hydrogen bonds among SA, glutaraldehyde and multi-active components of FW, resulting in enhanced water vapor barrier properties. The minimum water vapor permeability of the prepared LMF reached (8.23 ± 0.05) ✕ 10-12 g cm/(cm2·s·Pa) with 1.82 wt % of plasticizer, 0.74 wt% of crosslinker and a mass ratio of HTP-FW to SA of 3.56:1. The prepared LMF showed good mechanical properties and could maintain its integrity after spraying it on the soil surface for 31 days. In addition, it could effectively prevent the loss of soil moisture and heat, promote the seed germination of Chinese cabbage and achieve 89.14% of weight loss after burying in the soil for 27 days. This study provides a high value-added route to convert the FW to a hydrophobic LMF with superior properties, which addresses not only the problem of food waste but also the pollution of plastic mulching film.

The matrine derivate MASM inhibits astrocyte reactivity and alleviates experimental autoimmune encephalomyelitis in mice.

Astrocytes (AST) play an important role in the pathogenesis of neurological disorders, and their activation is involved in the progression of multiple sclerosis (MS). (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits vast pharmacological activities, such as anti-tumor, anti-fibrosis and immune regulation. In this study, we demonstrate that MASM is a promising agent for the treatment of experimental autoimmune encephalomyelitis (EAE). MASM not only inhibited inflammatory responses in LPS-stimulated astrocytes, but also suppressed the formation of reactive A1 astrocyte and maintained astrocytic functions, including the ability to promote synapse formation and phagocytose synapses and myelin debris. Importantly, MASM could significantly alleviate the development of EAE, with significant inhibition of inflammation, demyelination, axon loss and the body weight loss. Meanwhile, MASM also inhibited the activation of astrocytes and improved the function of BBB in vivo. These findings provide novel insights into the protective effect of MASM on EAE, which may be a promising drug candidate for treatment of EAE.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines. METHODS: Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software. RESULTS: Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group. CONCLUSION: Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China.

BACKGROUND: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China. METHODS: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests. RESULTS: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ2=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ2=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly. CONCLUSIONS: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.

Effect of Si-Miao-Yong-An decoction on the differentiation of monocytes, macrophages, and regulatory T cells in ApoE-/- mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Miao-Yong-An decoction (SMYAD) is a renowned traditional Chinese medicinal formula. SMYAD was originally recorded in the "Shi Shi Mi Lu", which was edited by medical scientist Chen Shi'duo during the Qing Dynasty. SMYAD has been traditionally used to treat thromboangiitis obliterans. At present, it is mainly used in clinical applications and research of cardiovascular diseases. AIM OF THE STUDY: To explore the effects of SMYAD on the pathological changes of atherosclerosis (AS) and the differentiation of monocytes, macrophages, and regulatory T (Treg) cells in apolipoprotein E knockout (ApoE-/-) mice. MATERIALS AND METHODS: Eight C57BL/6J mice, which were fed with normal diet for 16 weeks, were used as control group. Forty ApoE-/- mice were randomly divided into model group, atorvastatin group, SMYAD low-dose (SMYAD-LD) group, SMYAD medium-dose (SMYAD-MD) group, and SMYAD high-dose (SMYAD-HD) group. ApoE-/- mice were fed with western diet (WD) for 8 weeks, and the drugs were continuously administered for 8 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured by the esterase method. Morphological changes of the aortic sinus in mice were observed by hematoxylin-eosin (HE) staining, the lipid infiltration of the aorta and aortic sinus were observed by oil red O staining, and the spleen index was calculated. The proportion of Ly6Chigh and Ly6Clow monocyte subsets, macrophages, and their M1 phenotype, as well as Treg cells in spleen were measured by flow cytometry. The expressions of cluster of differentiation 36 (CD36), scavenger receptor A1 (SRA1), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), F4/80, and fork head frame protein 3 (FOXP3) in aortic sinus were assessed by immunohistochemical staining. The serum levels of oxidized low density lipoprotein (ox-LDL), interleukin-1ß (IL-1ß), IL-18, transforming growth factor-ß (TGF-ß), and IL-10 were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: Compared with the model group, the level of serum TC and LDL-C decreased in the SMYAD group, the pathological changes of aortic sinus decreased, and lipid infiltration of aorta and aortic sinus also decreased. These decreases were accompanied by a significant downregulation of CD36, SRA1, and LOX-1. Furthermore, the proportions of Ly6Chigh pro-inflammatory monocyte subsets, macrophages, and their M1 phenotypes in spleen decreased significantly, while the proportion of Treg cells increased. In addition, while the expression of F4/80 decreased, the expression of FOXP3 increased in the aorta sinus. The levels of serum pro-inflammatory factors IL-1ß and IL-18 decreased. CONCLUSIONS: SMYAD can improve the pathological changes associated with AS and can inhibit lipid deposition in ApoE-/- mice induced by WD diet. The likely mechanism is the inhibition of the differentiation and recruitment of monocytes and macrophages, the promotion of the differentiation and recruitment of Treg cells, as well as the reduction of the secretion of pro-inflammatory factors.

TMA/TMAO in Hypertension: Novel Horizons and Potential Therapies.

Hypertension is the most prevalent chronic disease and a risk factor for various diseases. Although its mechanisms and therapies are constantly being updated and developed, they are still not fully clarified. In recent years, novel gut microbiota and its metabolites have attracted widespread attention. It is strongly linked with physiological and pathological systems, especially TMA and TMAO. TMA is formed by intestinal microbial metabolism of choline and L-carnitine and converted into TMAO by FMO3. This paper collected and collated the latest researches and mainly discussed the following four parts. It introduced gut microbiota; provided a focus on TMA, TMA-producing bacteria, and TMAO; summarized the alternations in hypertensive patients and animals; discussed the mechanisms of TMAO with two respects; and summarized the regulatory factors may be as new interventions and therapies of hypertension. And, more relevant studies are still prospected to be accomplished between hypertension and TMA/TMAO for further clinical services.

Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain modulation technique that has been proved to exert beneficial effects in the acute phase of stroke. To explore the underlying mechanism, we investigated the neuroprotective effects of cathodal tDCS on brain injury caused by middle cerebral artery occlusion (MCAO). RESULTS: We established the MCAO model and sham MCAO model with an epicranial electrode implanted adult male Sprague-Dawley rats, and then they were randomly divided into four groups (MCAO + tDCS, MCAO + sham tDCS (Sham), Control + tDCS and Control + Sham group). In this study, the severity degree of neurological deficit, the morphology of brain damage, the apoptosis, the level of neuron-specific enolase and inflammatory factors, the activation of glial cells was detected. The results showed that cathodal tDCS significantly improved the level of neurological deficit and the brain morphology, reduced the brain damage area and apoptotic index, and increased the number of Nissl body in MCAO rats, compared with MCAO + Sham group. Meanwhile, the high level of NSE, inflammatory factors, Caspase 3 and Bax/Bcl2 ratio in MCAO rats was reduced by cathodal tDCS. Additionally, cathodal tDCS inhibited the activation of astrocyte and microglia induced by MCAO. No difference was found in two Control groups. CONCLUSION: Our results suggested that cathodal tDCS could accelerate the recovery of neurologic deficit and brain damage caused by MCAO. The inhibition of neuroinflammation and apoptosis resulted from cathodal tDCS may be involved in the neuroprotective process.