Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Compared with traditional drying methods for Chinese materia medica, microwave drying technology is not only with the features of easy and convenient to operate, rapidity, good effects, well remained appearance of medicine and low energy consumption, but also with the feature of extraordinary sterilization effects at the same time with drying. This article introduced the features and effects of microwave drying and sterilization technology, reviewed its application in the TCM field, and proposed existing problems and prospects in the recent research by targeting security problems (microwave radiation and microwave residue).

OBJECTIVETo address the features of the fungal infection after burn injury in clinic.

METHODSThree thousand nine hundred and nine burn patients admitted to our institute from Jan. 2003 to Dec. 2006 were involved in this study. Two thousand two hundred and seventy-one samples were harvested for fungal detection by culture from 467 patients suspected to be infected by fungi based on their clinic manifestations. The collected samples included wound tissue, blood, urine, stool, sputum, catheters and others. The antibiotic sensitivity of the identified fungi were determined by routine method. When same kind of fungus was found from different samples taken from one patient, it was recorded as one positive sample. The samples were ranked in an ascending order as wound secretion, stool, urine, sputum and bronchial alveolar lavage fluid, arteriovenous catheter or urinary catheter, blood. Only the positive sample of the highest rank source was recorded as the positive strain of fungus from this particular patient.

RESULTSIt was found 61 fungal positive samples from the 2271 samples collected. Out of 467 patients, 38 strains of fungi were detected from 36 burn patients during the investigated period, the incidence was 0.92% (36/3909). The most three commonest types among the identified 38 strains of fungi were Candida tropicalis (42.1%), Candida albicans (31.6%) and Candida famata (T. Famata, 10.5%). The drug sensitivity tests demonstrated that most of the strains detected in this investigation, with the exception of candida glabrata, were sensitive to most of the routine antimycotics agents such as Amphotericin B, Fluconazole, and Itraconazole etc. Among the 36 fungus positive patients, in 18 patients the burn area exceeded 80% TBSA, 12 patients with 50%-79% TBSA, 4 patients with 30%-49% TBSA, and in 2 patients the burn area was smaller than 30% TBSA. It was found most of the fungal infections (77.78%) occurred 2 weeks after burn injury, and 8 of the 36 fungus-infected patients died (the mortality was 22.22%). Conclusions Further examinations are necessary to confirm the diagnosis in burn patients suspected to have fungal infection. Once fungal infections are confirmed, antimycotic therapy must be started immediately.

Burns ; microbiology ; Candida ; isolation & purification ; Humans ; Incidence ; Microbial Sensitivity Tests ; Mycoses ; drug therapy ; pathology

Metabolic characteristics of 39 human brain tumor tissues, including 15 astrocytomas, 13 fibroblastic meningiomas and 11 transitional meningiomas from 39 individual patients, have been studied using high resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy in conjunction with principal component analysis (PCA). With rich metabolite information, 1H NMR spectra showed that the tumor-tissuc metabonome was dominated by lipids, lactate, myo-inositol, ereatine, choline metabolites such as choline, phosphocholine and glycerophosphocholine, amino acids such as alanine, glutamate, glutamine, taurine, N-acetyl-aspartate and glutathione. PCA of the tumor NMR spectra clearly showed metabonomic differences between low-grade astrocytomas and meningiomas whereas such differences were more moderate between fibroblastic and transitional meningiomas. Compared with meningiomas, the low-grade astrocytomas had higher levels of glycerophosphocholine, phosphocholine, myo-inositol and creatine but lower levels of alanine, glutamate, glutamine, glutathione and taurine. The N-acetyl-aspartate level was low but detectable in low-grade astrocytomas whereas it was not detectable in meningiomas. It is concluded that tissue metabonomics technology consisting of HRMAS 1H NMR spectroscopy and multivariate data analysis (MVDA) offers a useful tool (1) for distinguishing different types of brain tumors, (2) for providing the metabolic information for human brain tumors, which are potentially useful for understanding biochemistry of tumor progression.

OBJECTIVETo establish a canine model of severe smoke inhalation injury on unilateral lung, in order to observe the pathomorphological changes in the injured lung within 24 postburn hours (PBHs).

METHODSTwenty five mongrel dogs were employed in the study and randomized into 3 groups. The left lung was injured by inhaling smoke produced by burning sawdust with sparing the right lung with a breathing tube in 10 dogs in group A. A conventional model of smoke inhalation injury to bilateral lungs was reproduced in 8 dogs in group B, and dogs in group C not subjected to smoke inhalation served as controls. Hemodynamic changes, blood gas analysis and the pathophysiologic changes in the lungs were observed within 24 PBHs.

RESULTSAll of the dogs in groups A and C survived. Hemodynamic indices in the dogs in groups A and C remained stable without showing signs of systemic hypoxia. The arterial oxygen partial pressure in dogs of group A was 65 +/- 5 mm Hg, and the oxygen saturation in the mixed blood was 0.64 +/- 0.04 at 24 PBHs, and they were much lower than those in group C but higher than those in group B. The pathological changes in the injured side of the lungs in group A were similar to those in group B with high consistency, and the changes, though milder, could also be identified in the contralateral uninjured lung. Five dogs died in the group B within 24 hours after smoke inhalation and the survivors showed signs of multiple organ failure.

CONCLUSIONThe canine model of acute severe unilateral pulmonary smoke inhalation injury was reproduced reliably, and could be an ideal model for the study on smoke inhalation injury.

Animals ; Burns, Inhalation ; Disease Models, Animal ; Dogs ; Lung Injury ; chemically induced ; Male ; Random Allocation ; Smoke Inhalation Injury

OBJECTIVETo investigate the biological activities of the bronchoalveolar lavage fluid (BALF) harvested from dogs with smoke inhalation injury at early post injury stage.

METHODSBALF was harvested from normal dogs and those inflicted by smoke inhalation injury for the employment in the study. Ninety four Wistar rats were employed in the study and were randomly divided into A (n=28), B (n=29) and C (n=37) groups. The rats were perfused intra-tracheally with normal saline, BALF from normal dog and BALF from injured dog, respectively in A, B and C groups. Every 7 rats in each group were used before the perfusion as normal control. The rats in control group and those in A, B and C groups at 4, 12 and 24 hours after BALF perfusion were sacrificed. The survival rate and the pathomorphological gross and microscopic changes in pulmonary tissue in all groups were observed. In addition, the contents of prostaglandin F1alpha/thromboxane B2 (PGF1alpha/TXB2), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) in pulmonary tissue homogenization and the pulmonary capillary permeability were determined simultaneously.

RESULTSAll the rats in A and B groups survived, but nine in C group died before sacrificing. The BALF from dogs inflicted by smoke inhalation injury could cause rat lung exhibiting pathomorphological changes similar to those in rats inhaling smoke directly. The rat pulmonary tissue contents of PGF1alpha/TXB2 in A and B groups after the perfusion tended to increase, while that in C group decreased gradually (P <0.01). The rat pulmonary tissue contents of TNF-alpha and MPO content in A and B groups after the perfusion revealed no obvious change (P >0.05), while those in C group increased evidently at 4 hour after the perfusion and decreased thereafter (P <0.05-0.01). The pulmonary capillary permeability in C group was higher than that in A and B groups at 4 hour after the perfusion (P < 0.01).

CONCLUSIONThe BALF from canine lungs during the early stage of inhalation injury exhibited biological activities. The primary and secondary pulmonary injury could be prevented or ameliorated by massive pulmonary lavage during early post injury stage after smoke inhalation injury.

Animals ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; Dogs ; Lung ; pathology ; Male ; Rats ; Rats, Wistar ; Smoke Inhalation Injury ; pathology

Objective　To explore the feasibility and safety of massive lung lavage to dogs in the early stage after acute serious smoke inhalation. Methods　A total of 16 dogs were inflicted with smoke inhaled injury and then divided into group A (n=5) without lung lavage, group B (n=6) in which left lung lavage was followed by lavage on the right 30 min later, and group C (n=5) in which the interval of the lavages on the left and right lung was 4 h. Massive lung lavage was carried out in 1 h after the injury under the guiding fiberoptic bronchoscopy and a special ventilation jet was served to supply enough oxygen to the dogs. The stability of pulmonary function and blood circulation were observed at different time points in every group. Results　The average operating time of unilateral lung lavage was about 15 minuted and the liquid volume left in every lung after operation was from 100 ml to 140 ml when the total lavaging volume was kept in 250 ml. The changes of hemodynamic parameters were identical in Group B and Group C. Inhalation injury had certain negative effect while lung lavage almost had no effect on the blood circulation of the animals in 2 lavage groups. No serious cardiac arrythemia was found in them during the lavaging. Pulmonary function in Group C was better than that in Group B but worse than that in Group A. In the 2 lavaging groups, PaO2 remained higher than 9.33 kPa（FiO2=0.4）during and after the lavaging. Conclusion The ventilation mode and the lavage method introduced here ensure the safety of massive lung lavage in dogs with acute smoke serious inhalation injury.