ABSTRACT
Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), is still one of the significant threats to human life. In recent years, the continuous exploration of small molecule inhibitors represented by bedaquinoline has brought new vitality into the field of tuberculosis. However, small molecule inhibitors will inevitably occur acquired drug resistance during clinical medication. As a new pharmacological mechanism, targeted protein degradation (TPD) achieves efficacy by destroying rather than inhibiting protein targets. It might be an excellent strategy to develop anti-tuberculosis drugs based on the TPD concept to solve drug resistance. This article reviews the protein degradation pathways of Mtb, such as the Pup proteasome system and the ClpP-ClpC1 complex enzyme system. The future development of these strategies into TPD drugs was prospected and summarized.
ABSTRACT
AIM To investigate the improving effect of Suoquan Capsules (Linderae Radix,Alpiniae oxyphyllae Fructus and Dioscoreae Rhizoma) on mice with diabetic cystopathy and its mechanism of action.METHODS Sixty mice were randomly assigned into normal group (n =8) and model group (n =52);the diabetic models of the latter were induced by high-fat feeding combined with streptozotocin (STZ) injection,then modeled mice (n =32) were randomly divided into model,Mecobalamin Tablets,low-and high-dose Suoquan Capsules groups.The influences of Suoquan Capsules on fasting blood glucose (FBG),glycated serum protein (GSP) level and general conditions were observed.The bladder leak point pressure (BLPP) was determined.Histopathological staining was performed on urinary bladder.And the expressions of substance P and NK1 receptor were detected by double immunofluorescent staining.RESULTS There were no significant differences in FBG,GSP,body weight,food intake and water consumption among various groups.The high-dose Suoquan Capsules significantly decreased urine volume of mice.Compared with the model group,the treatment with Suoquan Capsules markedly increased BLPP,the expressions of substance P and NK1 receptor were significantly increased,and the histopathology of bladder in mice was obviously improved.CONCLUSION Suoquan Capsules improves the diabetic cystopathy in mice,and its mechanism maybe related to the up-regulation of substance P and NK1 receptor expressions in bladder tissue.
ABSTRACT
<p><b>OBJECTIVE</b>The study was designed to investigate the impact of non-dilated coronary artery wall lesion on myocardial perfusion.</p><p><b>METHODS</b>Doppler tissue image (DTI) was used to measure regional ventricular wall motion in 43 Kawasaki children with non-dilated coronary arterial wall echocardiographic abnormalities (rough intima and arterial wall thickening) detected by two-dimensional echocardiography (2DE) at acute phase. A total of 31 cases who had both non-dilated coronary lesion and lowered ventricular wall motion velocity at subacute and convalescence phase underwent submaximal exercise single photon emitting computerized tomography (SPECT) for the evaluation of myocardial perfusion.</p><p><b>RESULTS</b>In 43 cases of Kawasaki disease with non-dilated coronary arterial wall abnormalities, 36 cases (83.7%) still had such lesions at subacute phase and 32 (74.4%)at convalescence. At the same time, lowered regional ventricular wall motion (RVWM) was found in 34 cases at subacute phase and in 31 cases at convalescence. DTI and 2DE had a very good correlation in the detection of such abnormalities (chi(c)2 = 9.64, P < 0.01 in subacute period, and chi(c)2 = 7.14, P < 0.01 in convalescence). In 31 cases accepting SPECT, 17 were positive. A total of 22 ischemic regions were detected. Eighteen out of 22 cases having ischemic regions had abnormal RVWM on DTI. SPECT ischemic regions were significantly in accordance with lowered RVWM in ventricular septum and anterior wall (chi(c)2=5.07 and 7.48, P < 0.05 and P < 0.01, respectively) noted in DTI.</p><p><b>CONCLUSION</b>Non-dilated coronary arterial wall abnormality is one of the forms of coronary artery wall lesions which could reduce myocardial flow perfusion. Its clinical significance is worthy of attention.</p>