Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Cell-Penetrating Peptides ; chemistry ; Drug Delivery Systems ; Enzymes ; chemistry ; Humans ; Neoplasms ; drug therapy

Abdominal Neoplasms ; complications ; metabolism ; pathology ; surgery ; Adult ; Dendritic Cell Sarcoma, Follicular ; complications ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Ki-1 Antigen ; metabolism ; Leukocytosis ; complications ; metabolism ; pathology ; surgery ; Receptors, Complement 3b ; metabolism ; Receptors, Complement 3d ; metabolism ; Young Adult

AIM:To investigate the clinical effect of anti-vascular endothelial growth factor (VEGF) drugs combined with laser photocoagulation for diabetic macular edema (DME).METHODS: Totally 94 patients (141 eyes) with DME from June to December 2015 in our hospital were selected and randomly divided into combined group of 47 cases (68 eyes, ranibizumab combined with laser therapy) and the control group of 47 cases (73 eyes, laser treatment).The levels of best corrected visual acuity (BCVA), macular central retinal thickness (CRT), total macular volume (TMV) and macular edema level were compared between the two groups at different time after treatment.RESULTS: The mean values of BCVA in the combined group were higher than those in the control group at 2, 6 and 12wk, and the difference was statistically significant (P<0.05).At 2, 6 and 12wk after treatment, the CRT and TMV values of the combined group were lower than those of the control group, the difference was statistically significant (P<0.05).After treated for 12wk, patients with macular edema of combined group was 80.9% in mild level, 17.7% in moderate level, 1.5% in severe level, those of the control group was 60.0%, 31.5%, 5.5%, the difference between the two groups was statistically significant (P<0.05).CONCLUSION: The effect of anti-VEGF drugs combined with laser therapy for DME patients is better than that of single laser therapy alone.

OBJECTIVETo investigate the effect and mechanism of Tangyikang (TYK) for improving pancreatic islet beta cell function in patients with latent autoimmune diabetes mellitus in adults (LADA).

METHODSSeventy-four LADA patients were randomly assigned to two groups. The 37 patients in the treatment group were treated with TYK decoction (one dose consisted of red ginseng 10 g, milkvetch root 30 g, lilyturf root 15 g, wild weed 10 g, coptis root 15 g, cape-jasmine fruit 10 g, giant knotweed rhizome 10 g, safflower 10 g and moutan bark 10 g) combined with insulin therapy, and the 37 in the control group treated with insulin therapy alone, and the course for all was 3 months. Changes of glycosylated hemoglobin, index of pancreatic islet beta-cell function (delta CP(2h)/delta BS(2h)), serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were observed before and after treatment.

RESULTSAll the above-mentioned indexes were improved after treatment in both groups, the post-treatment data showed significant difference between groups in delta CP(2h)/delta BS(2h), (0.258 +/- 0.106 vs 0.168 +/- 0.054, higher in the treatment group, t = 4.626, P < 0.01), but with insignificant difference in glycosylated hemoglobin (t = 0.441, P = 0.660). Besides, the dosage of insulin used in the treatment group was less than that in the control group (t = -4.169, P < 0.01); covariance analysis showed, through excluding impact of different dosages insulin used, IL- 4 level was higher (F = 24.217, P < 0.01) and IFN-gamma level was lower (F = 14.198, P < 0.01) in the treatment group than those in the control group.

CONCLUSIONSTYK could improve the function of islet beta-cell, its possible mechanism is related with the regulation on cell immunity and the correction of T-lymphocyte subsets (Th1/Th2 ratio) imbalance.

Adult ; Diabetes Mellitus, Type 1 ; blood ; drug therapy ; immunology ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Islets of Langerhans ; drug effects ; immunology ; physiopathology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo investigate clinical effects and mechanism of Tangweikang (TWK) in treating diabetic gastroparesis.

METHODSNinety diabetic gastroparesis patients were randomly assigned to 3 groups. Besides conventional hypoglycemic treatment, the 30 patients in the treated group were given TWK and the 30 in the control group were given Domperidone additionally, while to the 30 in the blank group, no additional drug was given. The clinical efficacy and the changes in level of motilin and gastric emptying rate were observed.

RESULTSTWK showed significant effects in improving clinical symptoms of patients, increasing gastric emptying rate, promoting gastrointestinal kinetics, shortening gastric emptying time and was beneficial to the control of blood sugar, including the 2 h post-prandial blood sugar and fructosamine. The curative rate and total effective rate in the treated group were 63.33% (19/30) and 93.33% (29/30) respectively, significantly different to those in the control group 26.67% (8/30) and 63.33%, also different to those in the blank group 23.33% (3/ 30) and 10.00%, respectively (P < 0.01). The clinical efficacy in the treated group was superior to that in the other two groups.

CONCLUSIONTWK has favorable therapeutic efficacy in treating DGP.

Aged ; Antiemetics ; therapeutic use ; Diabetes Complications ; drug therapy ; Domperidone ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Gastroparesis ; drug therapy ; etiology ; Humans ; Male ; Middle Aged ; Phytotherapy ; Treatment Outcome

OBJECTIVETo discuss the effect of Taohong Siwu Decoction (TSD) in regulating functions of endothelial cells and treating arteriosclerosis obliterans (ASO).

METHODSThe ASO model was prepared by using high-fat diet plus intimal injury. They were randomly divided into the model group (n = 10), the normal control group (n = 9), the low dose TSD group (group A, n = 12), the middle dose TSD group (group B, n = 10), and the high dose TSD group (group C, n = 9). Eight weeks after modeling, the limb blood perfusion was observed using laser Doppler flowmetry. The arterial morphology was observed using light microscope and transmission electron microscope. The number of circulating endothelial cells (CECs) was determined using Percoll density gradient centrifugation method. Serum levels of TNF-alpha, IL-1, ET-1, and NO were detected using double antibody sandwich assay of enzyme linked immunosorbent assay (ELISA).

RESULTSThe ASO rat model was successfully established. Blood lipids levels significantly increased, the blood perfusion of left hind limbs significantly decreased, the number of CECs in the peripheral blood significantly increased, the arterial lumen was irregularly narrowed, the ultra-structure of vessel walls was damaged, serum levels of TNF-alpha, IL-1, and ET-1 significantly increased, and the serum level of NO significantly decreased in the model group, showing statistical difference when compared with the normal control group (P < 0.01). Compared with the model group, significant improvement in the aforesaid indices was shown in group B and C (P < 0.05, P < 0.01).

CONCLUSIONSThe injury and abnormal functions of endothelial cells is an important pathological process of ASO. As an effective recipe for treating ASO, TSD could protect vascular endothelial cells and improve the secretion function of vascular endothelial cells.

Animals ; Arteriosclerosis Obliterans ; blood ; drug therapy ; Diet, High-Fat ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelial Cells ; metabolism ; Endothelin-1 ; blood ; Endothelium, Vascular ; cytology ; Interleukin-1 ; blood ; Male ; Nitric Oxide ; blood ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood

Objective To detect the mutations of ATP2C1 gene in patients with Hailey-Hailey dis- ease (HHD).Methods PCR and direct sequencing were performed in 17 patients and 120 healthy controls to screen the mutations in the exons of ATP2C1 gene.Results Eight mutations were identified in nine probands, including three deletion mutations (nt1464-1487 del/nt1462-1485del,1523delAT,2375delTTGT),three splice site mutations (360—2A→G,1415—2A→T,2243+2T→C) and two missence mutations (C920T and G1942T).None of the above mutations was found in the controls.Conclusion Eight specific novel mutations were identified in nine probands of HHD,which could be causative factors of the disease.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.
Animals ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Dyslipidemias ; metabolism ; Energy Metabolism ; drug effects ; Fatty Liver ; chemically induced ; complications ; Female ; Fibroblast Growth Factors ; administration & dosage ; pharmacology ; therapeutic use ; Insulin Resistance ; Lipolysis ; drug effects ; Liver ; metabolism ; pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Sodium Glutamate

"Shengdeng" is its Tibetan transliteration referring to many medicines. Tibetan doctors and pharmacists in different areas use different drugs in formulation and clinical application, which are easily confused. In order to grasp the formula and clinical application accurately, we conduct a literature survey on history and current state of botanical origin and clinical application of "Shengdeng", making clear the application of various herbs named "Shengdeng" and providing reference to all Tibetan researchers and clinical workers in formulation and clinical application.
Drug Therapy ; history ; Drugs, Chinese Herbal ; analysis ; history ; therapeutic use ; History, Ancient ; Humans ; Medicine, Tibetan Traditional ; history ; Plants, Medicinal ; chemistry

OBJECTIVETo improve the knowledge of Kaposi sarcoma and the relationship between Kaposi sarcoma and human immunodeficiency virus (HIV) infection, and to improve the ability to diagnose and treat Kaposi sarcoma and acquired immune deficiency syndrome (AIDS).

METHODSSymptoms, signs and results of 121 patients encountered in the department of otorhinolaryngology head and neck surgery in Tanzania, who was diagnosed as Kaposi sarcoma actually with HIV infection and AIDS, were retrospectively analyzed in this study.

RESULTSThere were 46 males and 75 females with age ranged from 5 to 65 years, medium 30 year. The mucous membranes and skin lesions was the most commonly seen clinical manifestation in 121 cases, these lesions appeared as raised blotches or lumps that might be purple, brown, or red, early stages typical lesions began as flat or slightly raised colored spots. Among the cases reported here, 25 patients (20.66%) showed progressive nose blockage and nose bleeding and the purple-red new-grows were found in the nose of these patients. Fifteen patients (12.40%) had flat or slightly raised colored spots in their mucous membrane of mouth (palate or tongue), and in other 7 patients, purple small lumps were found in the gums of the patients. There were same lesions in their pharynx in 9 cases. In 10 patients (8.26%), Kaposi sarcoma was found in tonsil looked like tonsillitis with enlarged tonsils by two to three degree. Twelve patients (9.92%) had masses in the neck with no pain. Thirty-five patients (28.92%)had lesions of purple black nodules, including 10 patients who had the same lesions with ulcer formation in the nodules. All patients had been followed-up for at least two-years. Eighty-five patients passed away in one year, survival rate of one year was 21.48% (26/121), only 12 patients survived from the disease over two years, two years' survival rate was 9.92% (12/121).

CONCLUSIONSKaposi sarcoma is the characteristic disease for AIDS, mainly found on the membranes and skin. These lesions appears as raised blotches or lumps that may be purple, brown, or red, early stages typical lesions begin as flat or slightly raised colored spots. Patients who had kaposi sarcoma often died in a short-time without treatment.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; HIV Infections ; complications ; diagnosis ; Head ; pathology ; Humans ; Male ; Middle Aged ; Neck ; pathology ; Retrospective Studies ; Sarcoma, Kaposi ; complications ; diagnosis ; Survival Rate ; Tanzania ; Young Adult