MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway / 中国药理学通报

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

Versatile Use of Mycobacterium indicus pranii (MIP) Vaccine

Mycobacterium indicus pranii (MIP) earlier known as Mw is a soil-borne, non-pathogenic, saprophytic and rapidly growing strain of mycobacteria. MIP is approved as a vaccine/ immunomodulator for various indications including mycobacterium infections like leprosy in humans. Its administration has resulted in satisfactory clinical improvement, accelerated bacillary clearance, and increased immune responses to Mycobacterium leprae antigens, thereby shortening the full recovery time of the patients. It also shares its antigens with M.tuberculosis. In the last decade, RCTs have been done establishing immunotherapeutic properties of MIP in the treatment of leprosy, tuberculosis, warts and experimently in leishmaniasis. Through its immune inducing and cytotoxic property, it has also proved beneficial for human use especially in treating lung cancer. The beneficial role of it is also being explored in breast, cervical, oral, liver, and bladder cancers. Various studies on MIP have shown that it has immune-modulating properties in humans. The curiosity of the human mind has led to it being tried in Covid treatment trials. The results have shown that administering MIP has lowered inflammatory markers in Covid 19 patients, promising us for it to be a potential treatment option. More RCTs with a larger sample size should be done to establish this. Cytokine storm seen in bacterial sepsis is also decreased with MIP administration. Considering the encouraging results in hastening recovery in various diseases it appears that MIP is perhaps not being exploited to its fullest potential

The role of Notch signaling pathway in insulin regulation of endometrial cancer cell growth and apoptosis / 重庆医学

Objective To investigate the effects of Notch signaling pathway on proliferation of insulin-induced endometrial carcinoma cells and apoptosis related protein expression levels.Methods The endometrial carcinoma Ishikawa 3-H-12 cell line was primarily cultured and subcultured in vitro.Then,the cultured cells were divided into five groups:the control group (3 mL PBS was added into the group),the insulin group (cells were stimulated by 1 × 106 mol/L insulin) and MW167 groups (different doses of γ-secretase inhibitor MW167 pretreated with insulin stimulation).After 48 h culturation,inhibition of endometrial carcinoma cell growth of each group was measured by MTT-colorimetric method,the apoptosis-related proteins (Caspase-3,Caspase-8) and Notch1 protein expression levels of each group were determined by Western blot.Results Insulin can promote Notch1 protein expression in endometrial carcinoma cells,after 48 h insulin stimulation,the Notch1 protein expression level was significantly higher than that in the control group (P＜0.05).MW167 can inhibit insulin-induced Notch1 protein expression in a concentration-dependent inhibition manner.The absorbance at 570 nm (A570) of endometrial carcinoma cells cultured for 24,48 and 72 h in different groups were significantly different (P＜0.05).The A570 values in the insulin group at each time point were higher than those in the control group (P＜0.05),and the insulin-induced endometrial carcinoma cell proliferation reached its highest level at 48 h.MW167 inhibited insulin-induced endometrial carcinoma cells proliferation in a concentration-and time-dependent manner,and 20 μmol/L MW167 persistently inhibited insulin-induced proliferation of endometrial carcinoma cells at 48 h.Western blot analysis showed that expression levels of Caspase-3 and Caspase-8 protein in the insulin group at each time point were lower than those in the control group (P＜0.05),and MW167 promoted the expressions of Caspase-3 and Caspase-8 in a concentration-and time-dependent manner.Conclusion MW167 can suppress the insulin-induced endometrial carcinoma cells proliferation and promote the expression of related apoptotic proteins by inhibiting Notch signaling pathway,and induce apoptosis of endometrial carcinoma ceils.

The role of Notch signaling pathway in insulin regulation of endometrial cancer cell growth and apoptosis / 重庆医学

Objective To investigate the effects of Notch signaling pathway on proliferation of insulin-induced endometrial carcinoma cells and apoptosis related protein expression levels.Methods The endometrial carcinoma Ishikawa 3-H-12 cell line was primarily cultured and subcultured in vitro.Then,the cultured cells were divided into five groups:the control group (3 mL PBS was added into the group),the insulin group (cells were stimulated by 1 × 106 mol/L insulin) and MW167 groups (different doses of γ-secretase inhibitor MW167 pretreated with insulin stimulation).After 48 h culturation,inhibition of endometrial carcinoma cell growth of each group was measured by MTT-colorimetric method,the apoptosis-related proteins (Caspase-3,Caspase-8) and Notch1 protein expression levels of each group were determined by Western blot.Results Insulin can promote Notch1 protein expression in endometrial carcinoma cells,after 48 h insulin stimulation,the Notch1 protein expression level was significantly higher than that in the control group (P＜0.05).MW167 can inhibit insulin-induced Notch1 protein expression in a concentration-dependent inhibition manner.The absorbance at 570 nm (A570) of endometrial carcinoma cells cultured for 24,48 and 72 h in different groups were significantly different (P＜0.05).The A570 values in the insulin group at each time point were higher than those in the control group (P＜0.05),and the insulin-induced endometrial carcinoma cell proliferation reached its highest level at 48 h.MW167 inhibited insulin-induced endometrial carcinoma cells proliferation in a concentration-and time-dependent manner,and 20 μmol/L MW167 persistently inhibited insulin-induced proliferation of endometrial carcinoma cells at 48 h.Western blot analysis showed that expression levels of Caspase-3 and Caspase-8 protein in the insulin group at each time point were lower than those in the control group (P＜0.05),and MW167 promoted the expressions of Caspase-3 and Caspase-8 in a concentration-and time-dependent manner.Conclusion MW167 can suppress the insulin-induced endometrial carcinoma cells proliferation and promote the expression of related apoptotic proteins by inhibiting Notch signaling pathway,and induce apoptosis of endometrial carcinoma ceils.

Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for the treatment of extensive cutaneous warts.

Background: Multiple cutaneous warts in adults are often symptomatic, cosmetically disabling, and difficult to treat. Killed Mycobacterium indicus pranii (previously known as Mycobacterium w, popularly known as Mw) vaccine has earlier been investigated in genital warts with encouraging results. Objective: To evaluate the efficacy and safety profile of intralesional injected killed Mw vaccine for the treatment of extensive extragenital cutaneous warts. Methods: In this study, a retrospective analysis of medical records was performed in patients with cutaneous warts treated with intralesional Mw vaccine. Only patients with more than 5 extra‑genital warts, involving at least two body sites and which had not shown any signs of spontaneous regression over 6 months were treated with the vaccine. Results: Forty four patients were treated with intralesional Mw vaccine. The mean number of warts was 41.5 ± 25.7 with a disease duration of 3.1 ± 2.5 years. Complete clearance was achieved in 24 (54.5%) patients with a mean of 3.4 ± 1.1 intralesional injections. Cosmetically acceptable response to therapy (>75% clearance) was achieved in 37 (84.1%) patients. Wart response at distant sites was seen in 38 (86.3%) patients. Thirty‑six patients (81.8%) experienced mild therapy‑related side effects. Eighteen patients with complete response were followed up for 5.27 ± 1.7 months and none had recurrence of lesions. Conclusions: Killed Mw vaccine is safe and effective in the treatment of extensive cutaneous warts. Larger, preferably randomized controlled trials are needed to assess its efficacy vis a vis standard therapies for warts.

Capacidade de exercício e seu valor prognóstico no pós-operatório de cirurgia cardíaca / Physical exercise capacity and its prognostic value in postoperative cardiac surgery

INTRODUÇÃO: O valor prognóstico da capacidade de exercício em pacientes submetidos à cirurgia de revascularização miocárdica (CRM) necessita de esclarecimentos. OBJETIVOS: Avaliar a capacidade de exercício e o seu valor prognóstico em pacientes com doença arterial coronariana, submetidos à cirurgia de revascularização miocárdica eletiva. MATERIAIS E MÉTODOS: Foram avaliados 21 pacientes e 29 controles. Dois incremental shuttle walk test (ISWT) e dois testes de caminhada de 6 min (TC6) foram realizados randomicamente em dias alternados. A força de preensão manual (FPM) foi também avaliada. RESULTADOS: A FPM em valores percentuais (78,4 ± 16 vs. 97,2 ± 15%), o TC6 em metros (412 ± 79 vs. 601 ± 7 m) e em valores percentuais (72 ± 13 vs. 110 ± 11%) e o ISWT em metros (257 ± 90 vs. 517 ± 138 m) e em valores percentuais (53 ± 16 vs. 108 ± 16%) foram significativamente (p < 0,05) inferiores nos pacientes. Onze pacientes apresentaram complicações pós-operatórias (grupo C) e dez evoluíram bem (grupo SC). O grupo C apresentou idade mais avançada (57 ± 6 vs. 71 ± 7 anos; p < 0,05), FPM inferior (33 ± 6 vs. 41 ± 9 kgf) e ISWT inferior (208 ± 81 vs. 311 ± 66 m). Não houve diferenças significativas para o TC6. A regressão logística selecionou o ISWT como determinante do prognóstico dos pacientes (p = 0,04). CONCLUSÃO: Os pacientes à espera de CRM eletiva apresentam significativa redução da capacidade de exercício e o ISWT apresentou valor prognóstico significativo discriminando os pacientes com complicações pós-operatórias.

INTRODUCTION: The prognostic value of exercise capacity in patients undergoing coronary artery bypass grafting (CABG) needs clarification. OBJECTIVES: To assess exercise capacity and its prognostic value in patients with coronary artery disease undergoing elective CABG. MATERIALS AND METHODS: We evaluated 21 patients and 29 controls. Two incremental shuttle walk test (ISWT) and two tests of 6-min walk test (6MWT) were performed randomly on alternate days. The handgrip strength (FPM) was also evaluated. RESULTS: The FPM in percentages (78.4 ± 16 vs. 97.2 ± 15%), the 6MWT in meters (412 ± 79 vs. 601 ± 7 m) and percentage values (72 ± 13 vs. 110 ± 11%) and the ISWT in meters (257 ± 90 vs. 517 ± 138 m) and percentage values (53 ± 16 vs. 108 ± 16%) were significantly (p < 0.05) lower in patients. Eleven patients had postoperative complications (group C) and 10 had a good outcome (group SC). The group C showed significantly (p < 0.05), older age (57 ± 6 vs. 71 ± 7 years old), FPM lower (33 ± 6 vs. 9 ± 41 kgf) and ISWT lower (208 ± 81 vs. 311 ± 66 m). There were no significant differences for the 6MWT. Logistic regression analysis comparing the ISWT and 6MWT selected ISWT as a determinant of prognosis of patients (p = 0.04). CONCLUSION: Patients waiting for elective CABG have significantly reduced exercise capacity and ISWT had significant prognostic value discriminating patients with postoperative complications.

Characteristics of protein from red crab (Chionoecetes japonicus) shell by commercial proteases

This study was performed to examine the characteristics of protein of red crab (Chionoecetes japonicus) shell powder hydrolyzed by commercial proteases. Red crab shell was digested by commercial proteases, such as Protamex (P), Neutrase (N), Flavourzyme (F), Alcalase (A), Protease M (PM) and Protease A (PA). Protein yield analyzed by Biuret assay, absorbance at 280 nm and brix revealed that PA was the enzyme having the highest proteolytic activity. SDS PAGE showed that molecular weight of proteins produced by protease treatments was various and below 150 kDa. Combinational treatment of proteases (PA + P, PA + PM, PA + F, PA + A) was tried whether these increase protein hydrolysis from red crab shell powder compared to a PA single treatment. Soluble protein content was similar, but amino acid concentration by combinational treatments was higher than PA single treatment [PA + P 247.4 mg/g > PA + F (206.4 mg/g) > PA + A (133.4 mg/g) > PA + PM (59.1 mg/g) > PA (54.9 mg/g)]. Amino acid composition by combinational treatments was slightly different. Most abundant essential amino acids were phenylalanine, glycine, alanine, and leucine, whereas tyrosine and cystine were not detected.

A retrospective study of intravenous sodium stibogluconate alone and in combinations with allopurinol, rifampicin, and an immunomodulator in the treatment of Indian post-kala-azar dermal leishmaniasis.

Background and Aims: A retrospective analysis of treatment outcome using recommended dose of sodium stibogluconate (SSG) alone and in combination with other antileishmanial drugs in adults with post-kala-azar dermal leishmaniasis (PKDL) attending as outpatients. Methods: A total of 61 patients seen over ten years were included in the report. All had polymorphic lesions. Diagnosis was based on clinical picture, hailing from kala-azar (KA) endemic area, exclusion of other dermatoses, histopathology, and therapeutic response. Patients were distributed into two groups: Group I (n = 32), where SSG was given intravenously; in Group II (n = 29), they were allocated to one of four categories using SSG in combination with other drugs. In the first category, SSG was given along with allopurinol (n = 10); in second with rifampicin (n = 6); and in third with both allopurinol and rifampicin (n = 5). In the fourth category, SSG was administered with an immunomodulator (n = 8), Mw vaccine, known to enhance host Th1 response. Results: Only 12 out of 61 patients completed treatment till histopathologic evidence of cure, five in Group I and seven in Group II, no patient being from third category. None had taken SSG without interruptions. Time taken for papulonodules to subside was similar in both groups, but erythema and induration subsided earlier in Group II. Group I patients attained cure after 120 injections while in Group II it took 95 injections in SSG + allopurinol and Mw vaccine categories respectively, and 110 with SSG + rifampicin. Nevertheless this was insufficient to facilitate compliance. Poor performance and high dropouts related to long duration of therapy, thrombophlebitis, difficulty in accessing veins, disabling rheumatic side-effects and practical problems. Liver, renal and pancreatic functions and ECG remained normal. Conclusion: No major advantage was obtained using allopurinol, rifampicin or Mw vaccine along with SSG as compared to SSG alone.

The Effects of Photodynamic Therapy with Photogem and Laser with Power Density of 600 mW/cm2 on Lewis Lung Carcinoma Cells Tumor Graft in Mouse

PURPOSE: Photodynamic therapy was used to lung cancer. We have made a light microscpic study on the effects of photodynamic therapy to tumor graft in skin of mice, when the power density was 600 mW/cm2 with reducing time. MATERIALS AND METHODS: These studies had been performed on sixteen C57BL/6 mice that Lewis lung carcinoma cells had been implanted. All mice were divided into four groups. One of four groups received Photogem 3 mg/kg intravenously 24 hours prior to exposure of tumor to 180 J/cm2 laser light vertically at a wavelength 635etam with a higher power density of 600 mW/cm2 than that of 400 mW/cm2 clinically. One of these group received only Photogem. The others not received Photogem and one of these irradiated with laser. The light source was the wavelength of 635 etam Diode Laser (Laxcell 2004, Bio- Optics. co. Korea) After photodynamic therapy was finished, staining and analysing of tumors were used to determine the natures and extents of injury. RESULTS: Grossly response was not observed. Histologically, there were loss of endothelium from small vessel at tumor and muscle with thrombus formation. There were focal necrosis with infiltration of inflammatory cells at tumor and adjacent tissues that irradiated with laser, regardless of administration of Photogem. CONCLUSION: Photodynamic therapy using Photogem and LASER with power density of 600 mW/cm2 destroy not only tumors incompletely but also adjacent normal tissue.

Interfacial reaction of microwave radiating field upon lamellar materials / 第三军医大学学报

Objective To explore the rule of energy distribution on the interfaces between lamellar materials,especially the dependence upon the radiating directions for a microwave(MW) radiation and to get some experimental evidences for further research of the shielding and protective mechanism of biological effects of MW.Methods Some MW shielding lamellar materials elaborately chosen,including fiber & metal wires intertexture,MW exposure suit materials by chemical treatment,nano-carbon coated metal sheets and fresh pigskin treated as biological tissue material,were exposed to the defined frequency(9.3 GHz) MW field and the characteristics of MW interfacial reactions upon the materials were detected by a micro-spectrometer.Results The fiber & insulated metal wires intertexture did not possess obvious MW-shielding function.The MW exposure suit materials by chemical treatment were strong reflecting type MW-shielding materials.The nano-carbon coated metal sheets had a "transparent window" for a rather wide range of MW incidence angles and so were used as MW secret materials.As biological tissue material,the fresh pigskin treated was identified as a kind of complex MW absorbing and reflecting material.Otherwise,the interaction between MW and biological material interfaces might vary regularly as the change in water-content occurred by the MW heating effect.Conclusion Although all the kinds of experimental samples exhibited the coherence with the reflection law to MW sheaf,there was plenty of significant diversity in detail nearby the MW reflecting region.The experimental evidence might be of characteristic classification for interaction between MW directional radiation and different material interfaces.Otherwise,as skin tissues absorb microwave rather sharply in little incident angles,this part of radiations should be considered more in the protective mechanism of MW.

Characterization of cytoplasmic Form of Human CTLA - 4 Molecule / 대한면역학회지

CTLA-4 (=CD152), a T cell activation antigen, has been known to be homologous to CD28 in its molecular and genomic structure. Both of these two molecules are sharing their counterreceptors, B7 (CDSO) and B7-2 (CD86) and are known to play a crucial role in T cell activation. In previous our study it was reported that there are 2 forms of CTLA-4 antigen in activated human T cells, 30 kD membrane-bound form and 34 kD cytosolic-sequestered form and the former was less than 5 % of total of this antigen induced. Aims of this study are to confirm previous finding by using flow cytometry and to characterize the cytoplasmic form of human CTLA-4 by using ultrafiltration and immunoprecipitation techniques. In PHA stimulated peripheral blood lymphocyte surface expression of CTLA-4 was less than 2.1% of any of CD4+, CD8+ and CD56+ subsets. And the 34 kD form of CTLA-4 was detected in CDS+ subset only. This discrepancy confirms that 34 kD antigen is the cytoplasmic form of human CTLA-4. In ultrafiltration and subsequent Western blot analysis study this 34 kD antigen was detected in >100 kD fraction only. And in non-reducing condition this antigen formed high molecular weght complex (MW > 350 kD). In immunoprecipitation study using anti-peptide A antibody it was found that this high molecular weight complex consists of the 34 kD cytoplasmic form of CTLA-4 and previously unknown 54 kD antigen and 46 kD antigen at 1:1:8-10 ratio. And none of these 3 molecules were identified in membrane fraction of activated human T cell. The result of this study implies that CTLA-4 molecule induced upon T cell activation mainly sequestered in cytoplasrn and another signal is necessary to target this antigen on the activated T cell surface.