Advances in targeted delivery of proteolysis targeting chimeras in cancer therapy / 生物工程学报

Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are "undruggable". Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.

The efficacy and safety of posterior retroperitoneoscopic adrenalectomy in the prone position / 中华泌尿外科杂志

Objective:To explore the efficacy and safety of posterior retroperitoneoscopic adrenalectomy (PRA) in the prone position.Methods:The clinical data of 74 patients who underwent PRA in the prone position in our hospital from January 2019 to February 2021 were reviewed. There were 36 males and 38 females, with an average age was (54.4±12.5) years old. The body mass index was (24.03±3.5) kg/m 2. CT scans of the adrenal glands were performed before operation. There were 39 cases of adrenal tumors on the left side, 33 cases on the right side, and 2 cases on both sides. The diameter of adrenal tumors shown on CT was (2.4±1.3) cm. Among them, 22 cases were diagnosed of non-functional adrenal tumors, 21 cases were primary aldosteronism, 8 cases were Cushing syndrome, and 23 cases were pheochromocytoma . The PRA in the prone position were performed in all 74 patients(76 sides). Results:The operation was performed successfully in all 74 patients(76 sides), of which 42 cases underwent unilateral adrenalectomy, 30 cases underwent unilateral partial adrenalectomy and 2 cases underwent bilateral adrenalectomy. The operation time was (53.2±16.1) min for 76 sides, and the time of two bilateral cases was 70 min and 115 min respectively. The median time of rainage tube indwelling was 3(0, 4) d, and the hospital stay was (4.2±0.9) d. The pathological diagnosis: there were 32 cases of adrenal cortical adenoma, 8 cases of adrenal cortical hyperplasia nodule, 5 cases of adrenal cyst, 7 cases of adrenal medullary lipoma, and 22 cases of adrenal pheochromocytoma. No adverse complications occurred during the perioperative period. The patients were followed-up for (12.5±2.7) months, and no tumor recurrence or long-term complications occurred.Conclusions:Posterior retroperitoneoscopic adrenalectomy in the prone position has the advantages of reducing bleeding and exudation, and rapid recovery after surgery, which provides a safe and effective surgical method for the treatment of adrenal tumors.

Molecular genetics of juvenile idiopathic arthritis and clinical significance / 中华实用儿科临床杂志

Juvenile idiopathic arthritis (JIA) is the most common disease in chronic rheumatic disorders,and also the major disability-causing disease in childhood.It is known that genetics may play a definite role in the pathogenesis of JIA.With the application of molecular genetics technology to JIA study,a panel of JIA-susceptible or-related genes have been revealed,among of which human leukocyte antigen loci demonstrate the highest risk correlation.JIA genetics also presents heterogenicity to some extent as with clinical heterogenicity,some of which have demonstrated certain clinical significance in evaluation of the outcome of JIA.However,more noteworthily,the current knowledge on JIA genetics may provide useful clue to future research of JIA.The review focuses on current progression and future issues in the study of JIA genetics,and thereby helps understand the pathogenesis of JIA and predict the clinical outcome.

Effect of chitosan on vascular smooth muscle cells inhibiting proliferation from rabbit arteriovenous fistula and its mechanisms / 中华显微外科杂志

Objective To explore the effect of chitosan on vascular smooth muscle cells inhibited proliferation from rabbit arteriovenous fistula and its mechanisms.Methods Established rabbit fistula model on carotid arteryinternal jugular vein.After 1 month cultured VSMCs with primary culture by tissue-pieces inoculation.Cultured VSMCs were divided into three groups:①normal control group.②FBS-treated group:cell were treated with 5％,10％,20％ for 48 h,respectively; established the model of rabbit VSMCs proliferation.③chitosan-treated group:VSMCs cultured with 20％ FBS were exposed to different doses of chitosan(10,100,500,1000,2000μg/ml) for 48 h.And VSMCs were treated for different time (0,12,24,48 h) with Chitosan 1000 μg/ml.Expression levels of PCNA and TLR4/ NF-κB were detected by Western blotting.RT-PCR were applied to measure the mRNA expression of PCNA and TLR4.The protein levels of TLR4 and NF-κB were detected by immunofluorescence.Results Compared with low concentration serum group,FBS-treated VSMCs exhibited a increase in mRNA and protein expression of PCNA and TLR4.FBS-induced protein expression of PCNA and TLR4/NF-κB were reduced by chitosan.Also mRNA expression of PCNA and TLR4 were reduced.They were dependent on concentration and time.In rabbit VSMCs TLR4 was mainly expressed in the cytoplasm and NF-κB expressed mainly in the nucleus.Compared with normal control group,TLR4 and NF-κB protein expression were significantly decreased by chitosan.Conclusion High concentration serum induced VSMCs proliferation.Chitosan can inhibit the proliferation of rabbit VSMCs.It is speculated that the mechanism may be related to the expression of TLR4 receptor activation,reducing expression of downstream factor MyD88 and NF-κB.It is suggest that chitosan can become potential new drugs of arteriovenous fistula prevention of intimal hyperplasia.

The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistocytosis / 中华内科杂志

Objective To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. Methods From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. Results Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11,XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH( EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH),1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t ( 15; 17 ) (q22; q25 ) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. Conclusions Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH,some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.

Changes of metabolic index of diabetes before and after Ramadan / 国际中医中药杂志

Objective To investigate changes of metabolism of glucose and lipoids in diabetes before and after Ramadan. Methods A total of 65 Muslim fasting diabetic patients, with complete data, were investigated about their diet and administrated medicines before and after the fasting and occurrence of hypoglycemia during the fasting. Indexes of WEIGHT, WAISTLINE, BMI, FPG, 2h-PG, HbA1c, TG, TC, HDL-C, and LDL-C were evaluated by questionnaire, physical examination and laboratory tests. Results During Ramadan, fasting time was prolonged (P＜0.01), intake of lipoids and protein were increased obviously (P＜0.01) and a significant increase of 2 h-PG, HbA1c (P=0.0149, 0.0175) was detected after Ramadan in s fasting group. No significant difference was found in WEIGHT, WAISTLINE, BMI, TG, TC, HDL-C, and LDL-C. Blood glucose was improved significantly in the control group than the fasting group. Conclusion Life style was changed obviously leading to unsatisfactory controlling of blood glucose in Muslim diabetic patients during Ramadan.

Autophagy Induced by NGAL Protein in Esophageal Carcinoma Cells / 生物化学与生物物理进展

Previous studies suggest that NGAL (neutro phil gelatinase-associated lipocalin) is involved in the transformation and development of esophageal carcinoma. Alteration of NGAL expression can trigger the change of cellular morphology in esophageal carcinoma cells. However, the mechanisms remain unclear. To get a better understanding of NGAL function in esophageal carcinoma, NGAL protein was expressed in methylotrophic yeast, Pichia pastoris, and purified by chromatography. EC1.71 cells expressed high levels of NGALR (NGAL receptor) and EC109 cells expressed low levels of NGALR were used as cells model. The trafficking and the possible function of NGAL protein were then analyzed in the esophageal carcinoma cells. The results showed that 5-FAM-labeled recombinant NGAL protein could internalize into the EC1.71 and EC109 cells. Furthermore, the internalized NGAL protein could induce the alteration of cellular morphology, resulting in generation of autophagosome, transcriptional up-regulation of genes associated with autophagy and increase of phospho-ERK1/2 (p-ERK1/2). Interestingly, the treatment with the NGAL protein did not affect the intracellular iron level. These data indicate that induced autophagy by exogenous NGAL protein is a mechanism that internalized NGAL plays important roles in esophageal carcinoma cells, independent with NGAL-mediated iron transport process, while ERK1/2 signal pathway is involved in activation of autophagy by exogenous NGAL protein.

Advances in research on relation of ubiquitin-proteasome pathway to malignancy / 中国癌症杂志

Ubiquitin-proteasome pathway is an important mechanism regulating many processes of cellular biology,and also a potential target for abnormal regulation associated with malignancy. This pathway may up-regulate or down-regulate the expression of some tumor-inhibitory genes, transcriptional factors and cyclins,and alter the generation of MHC-I-restricting antigen peptides through the activity of specific proteasome, and consequently,participates in the genesis and progression of malignancy.

Hypoxia-reoxygenation induced apoptosis of cardiomyocytes and the effect of nitric oxide / 中国药理学通报

AIM To study hypoxia reoxygenation induced apoptosis of neonatal rat cardiomyocytes and the roles of nitric oxide in this process. METHODS Cultured neonatal rat cardiomyocytes were divided into two groups. Cells of one group were cultured in an incubator of 950 mL?L -1 N 2 and 50 mL?L -1 CO 2 for 16 h, 32 h and 48 h followed by normal incubation for 6h to form the cell model of hypoxia reoxygenation injury.Cells of another group were cultured in the same hypoxia condition for 16 h, 32 h and 48 h. Before they were put in normal condition for 6 h, NO donor SNAP was added to the media to form the final concentration of 100 ?mol?L -1 . Apoptosis was detected by TUNEL and flow cytometer. RESULTS Apoptotic cells were detected by TUNEL after hypoxia of 16 h, 32 h and 48 h followed by 6 h reoxygenation and the apoptotic rates of cardiomyocytes were (5 5?0 7)%, (11 0?1 1)% and (14 2?1 6)% respectively detectedby flow cytometer. The apoptotic rates of myocardiums with SNAP were (3 2?0 7)%, (7 8?0 7)% and (10 9?1 0)% respsctively. CONCLUSION The apoptotic rates of cardiomyocytes undergoing hypoxia reoxygenation injury increase with time of hypoxia; NO can inhibit apoptotic rates of cardiomyocytes in this pathological process and thus may have a protective effect on cardiomyocytes.