The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on β-amyloid protein 25-35(Aβ_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aβ_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of β-amyloid protein 1-42(Aβ_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aβ_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol with β-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aβ_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aβ_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aβ_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aβ_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aβ_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.
Mice ; Male ; Animals ; Alzheimer Disease/drug therapy* ; Amyloid beta-Peptides/metabolism* ; Cornus/metabolism* ; Neuroinflammatory Diseases ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; Aspartic Acid ; Cysteine/therapeutic use* ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Brain Injuries ; Peptide Hydrolases ; Disease Models, Animal ; Mice, Transgenic

OBJECTIVE: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. METHODS: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. CONCLUSION The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Animals ; China ; Cysteine-Rich Protein 61/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod/adverse effects* ; Inflammation/drug therapy* ; Intercellular Adhesion Molecule-1/genetics* ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Psoriasis/pathology* ; RNA, Messenger/therapeutic use*

OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.
Antiviral Agents ; chemistry ; therapeutic use ; Betacoronavirus ; chemistry ; enzymology ; Coronavirus Infections ; drug therapy ; prevention & control ; virology ; Cysteine Endopeptidases ; chemistry ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Mass Spectrometry ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; prevention & control ; Pneumonia, Viral ; drug therapy ; prevention & control ; virology ; Protein Interaction Maps ; Viral Nonstructural Proteins ; chemistry

While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.
Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Cysteine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Disease Models, Animal ; Garlic ; chemistry ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; metabolism ; Signal Transduction ; drug effects

OBJECTIVE: This study aims to use Arginine-gingipain A gene vaccine (pVAX1-rgpA) to immunize adult Beagle dogs and to evaluate its effect during peri-implantitis progression and development. METHODS: Plasmid pVAX1-rgpA was constructed. The second and third bilateral mandible premolars of 15 adult Beagle dogs were extracted, and the implants were placed immediately. After 3 months, the animals were randomly divided into groups A, B, and C. Afterward, the animals were immunized thrice with plasmid pVAX1-rgpA, with heat-killed Porphyromonas gingivalis, or pVAX1, respectively. IgG in the serum and secretory IgA (sIgA) in saliva were quantitatively analyzed by enzyme-linked immunosorbent assay before and after 2 weeks of immunization. Peri-implantitis was induced with cotton ligatures fixed around the neck of implants. Probing depth (PD) and bleeding on probing were recorded. All animals were sacrificed after ligaturation for 6 weeks. Decalcified sections with thickness of 50 μm were prepared and dyed with methylene blue to observe the bone phenotype around implants. RESULTS: Levels of serum IgG and sIgA in saliva were higher in groups A and B after immunization than before the process (P<0.05) and higher than those in group C (P<0.05). However, no difference was observed between groups A and B (P>0.05). At 4 and 6 weeks after ligaturation, PD of the ligatured side in group C was higher than that in groups A and B (P<0.05). On the other hand, no difference was identified between groups A and B (P>0.05). Bone loss in group A was significantly lower than that of the other groups (P<0.05). Abundant inflammatory cells and bacteria were present in the bone loss area around the implants in the three groups, as identified through hard tissue section observation. However, group C presented the most number of inflammatory cells and bacteria in the bone loss area around the implants. CONCLUSIONS IgG and sIgA can be generated by immunity with rgpA DNA vaccine, which can significantly slow down bone loss during experimental peri-implantitis in dogs.
Adhesins, Bacterial ; therapeutic use ; Alveolar Bone Loss ; Animals ; Arginine ; Cysteine Endopeptidases ; therapeutic use ; Dental Implants ; Dogs ; Peri-Implantitis ; prevention & control ; Porphyromonas gingivalis ; chemistry ; Vaccines ; therapeutic use

OBJECTIVETo compare the efficacy and safety of Stronger Neo-Minophagen C (SNMC) in the treatment of chronic hepatitis B.

METHODSWe searched MEDLINE, EMBASE, CBM, and CNKI up to December, 2012 to identify randomized controlled trials (RCTs) comparing Stronger Neo-Minophagen C plus other therapy versus others therapy for chronic hepatitis B. Two reviewers independently assessed the risk of bias and extracted data from the included RCTs according to the Cochrane Reviewers Handbook 5.1.0. Meta-analyses were performed using RevMan 5.1 software.

RESULTSThirty-one trials involving 2753 patients were included in the analysis. The results of meta-analyses showed that SNMC improved hepatic functions of the patients by reducing ALT (MD=-31.63, 95% CI: -51.57, -11.70), AST (MD=-18.70, 95% CI:-25.10, -12.30), TBIL (MD=-12.17, 95% CI: -17.63,-6.71), HA (MD=-94.89, 95% CI: -125.19, -64.60), LN (MD=-40.08, 95% CI: -52.38,-27.78), IV-C (MD=-50.61, 95% CI:-63.40, -37.81), PC-III (MD=-49.71, 95% CI: -71.72, -27.69) as compared with the control group. The seroconversion rate of HBeAg (OR=2.23, 95% CI: 1.70, 2.94), HBV-DNA (OR=2.20, 95% CI: 1.70, 2.84), HBsAg (OR=2.25, 95% CI: 1.24 , 4.07), total response rate (OR=4.37, 95% CI: 2.62, 7.28), and ALT normalization rate (OR=3.77, 95% CI: 2.46, 5.79) were all significantly higher in the combined therapy group than in the control group.

CONCLUSIONSNMC plus other therapy is more effective than other therapy alone in improving the hepatic function and hepatic fibrosis and increasing hepatic seroconversion rate in patients with chronic hepatitis B without causing serious adverse events. But considering the low quality of the included studies, the results should be interpreted with caution and awaits further confirmation by high-quality, large-scale RCTs.

Cysteine ; therapeutic use ; Drug Combinations ; Glycine ; therapeutic use ; Glycyrrhetinic Acid ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; Randomized Controlled Trials as Topic

BACKGROUNDNon-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.

METHODSA SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.

RESULTSVEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1 by siRNA was associated with decreased VEGF expression. SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%, 38.2%, and 58.2% in high, moderate and low differentiated tumors, respectively, P = 0.046), higher T stage (10.9% in T1, and 89.1% in T2 and T3 tumor samples, P < 0.001) and TNM stage (10.9% in stage I, and 89.1% in stages II and III tumor samples, P < 0.001). The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%, P < 0.001). Sixty three patients received postoperative chemotherapy, including 34 with SENP1 over-expression and 29 with SENP1 low expression. Among the 34 patients with SENP1 over-expression, 22 (64.7%) patients developed recurrence or metastasis, significantly higher than those in the low expression group 27.6% (8/29) (P = 0.005). Multivariate Cox regression analysis showed that lymph node metastasis (P = 0.015), TNM stage (P = 0.001), and SENP1 expression level (P = 0.002) were independent prognostic factors for the survival of NSCLC patients.

CONCLUSIONSSENP1 may be a promising predictor of survival, a predictive factor of chemo-sensitivity for NSCLC patients, and potentially a desirable drug target for lung carcinoma target therapy.

Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Cell Line, Tumor ; Cysteine Endopeptidases ; Endopeptidases ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Male ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To investigate the protective effect of celastrol on allergic rhinitis rats and its possible mechanism. METHOD: Allergic rhinitis (AR) model of rats was established by OVA. The behavioural characteris tics were observed at the 1st, 4th and 7th dayafter stimulation treatment. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-PX) in the nasal mucosa breathing zone were measured. The expression of the nuclear factor erythroid 2 related factor 2 (NRF2) nuclear protein and the catalytic submit of glutamylcysteine ligase (GCLC) cytoplasmic protein in the nasal mucosa breath ing zone were determined. RESULT: We observed obvious behaviour changes related with allergic rhinitis in AR rats, together with decrease of SOD, GSH and GSH-PX and increase of MDA in the nasal mucosa breathing zone. Moreover, NRF2 nuclear protein expression and GCLC cytoplasmic expression were suppressed in the nasal mucosa. The changes above were alleviated in celastrol pretreatment group. The potential mechanism may be related to the upregulation of NRF2 nuclear protein expression and GCLC cytoplasmic expression after celastrol pretreatment. CONCLUSION Celastrol can significantly relieve the allergic symptoms in AR rats. The mechanism of this protective effects may relate to the upregulation of NRF2 nuclear protein expression and GCLC cytoplasmic expression in the nasal mucosa breathing zone.
Animals ; Disease Models, Animal ; Glutamate-Cysteine Ligase ; metabolism ; Male ; NF-E2-Related Factor 2 ; metabolism ; Nasal Mucosa ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic ; drug therapy ; Triterpenes ; therapeutic use

Acetates ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; etiology ; metabolism ; Bronchiolitis, Viral ; drug therapy ; Cysteine ; metabolism ; Humans ; Infant ; Infant, Newborn ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Leukotrienes ; biosynthesis ; Nasopharynx ; secretion ; Quinolines ; administration & dosage ; therapeutic use ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; virology ; Risk Factors

OBJECTIVETo observe the effects of comprehensive therapy on serum secreted protein acidic and rich in cysteine (SPARC) levels in ankylosing spondylitis (AS) patients accompanied with osteoporosis (OP), and to explore the possible mechanisms for SPARC in AS patients accompanied with osteoporosis.

METHODSTotally 48 AS patients accompanied with OP (Group A) were treated with massage, intravenous infusion of Cervus and Cucumis Polypeptide Injection, and Bushen Quhan Zhiwang Decoction (BQZD) for 3 months. At the same time, 45 normal healthy subjects were recruited as the normal control group (Group B). Serum SPARC levels were measured by ELISA in Group A before and after comprehensive therapy and in those of Group B. The levels of bone mineral density of femoral neck (FN BMD), bone mineral density of 2 -4 lumbar spine (L2-4 BMD), bone specific alkaline phosphatase (BSAP), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta-1 (TGF-beta1) were detected. Meanwhile, Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) were detected in Group A before and after treatment. The correlations between the aforesaid indices and serum SPARC levels were analyzed.

RESULTSSerum SPARC levels were significantly lower in those of Group A than in those of Group B (175. 30 +/- 72.04 micro/L vs 190. 52 +/- 86. 13 microg/ L, P <0. 01). Serum SPARC levels in those of Group A were negatively correlated with TNF-alpha (r = -0.261, P <0.01), positively with L2-4 BMD, TGF-beta1, and BSAP (r =0.437,0.256, 0.385, P <0.05, P <0.01). L2-4BMD and BSAP were independently predictors of serum SPARC in patients of Group A. After comprehensive therapy, the levels of TNF-alpha, BASDAI, and BASFI obviously decreased, TGF-beta1, BSAP, L2-4 BMD, and FN BMD obviously increased (P <0. 05, P <0. 01). The serum SPARC levels also significantly increased (188.32 +/- 87.50 microg/L, P <0. 05).

CONCLUSIONComprehensive therapy could effectively improve the bone metabolism, clinical symptoms and the activity function of joints, and elevate serum SPARC levels.

Adolescent ; Adult ; Bone Density ; Case-Control Studies ; Combined Modality Therapy ; Cysteine ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteonectin ; blood ; Osteoporosis ; blood ; complications ; therapy ; Spondylitis, Ankylosing ; blood ; complications ; therapy ; Young Adult