Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Objective To investigate the mechanism of Sini San Formula in the treatment of ulcerative colitis and depression through"homotherapy for heteropathy"based on network pharmacology and molecular docking.Methods The TCMSP database was used to obtain the potential active components and their related targets;GeneCards,CTD,and TTD databases were used to screen the disease-related targets of ulcerative colitis and depression;the intersection of the predicted targets of the active components and the disease-related targets was used to obtain the potential targets(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,and Cytoscape 3.7.2 software to construct a"Chinese medicinals-active components-diseases-common targets"network to analyze the core components;importing the common targets into the STRING database,constructing a common protein-protein interaction(PPI)network.The GO function and KEGG pathway enrichment of the shared targets were analyzed by DAVID database,and molecular docking between the core components and the key targets was verified.Results A total of 136 active components of Sini San Formula were obtained,and 220 potential targets of action(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,involving 657 biological processes,70 cellular components,147 molecular functions and 133 signaling pathways.The screening yielded core active compounds such as quercetin,kaempferol,lignans,naringenin,7-methoxy-2-methylisoflavone,key target proteins such as JUN,MAPK3,STAT3,AKT1,and MAPK1,as well as signaling pathways such as TNF,IL-17,Th17 cellular differentiation,HIF-1,and Toll-like receptor.Five potential key targets have strong binding activity to quercetin,kaempferol,lignans and naringenin.Conclusion Sini San Formula may act on key targets such as JUN,MAPK3,STAT3,AKT1,MAPK1,etc.through active components such as quercetin,kaempferol,lignocerotonin,naringenin,etc.,and play the role of"homotherapy for heteropathy"for ulcerative colitis and depression through the signaling pathways such as TNF,IL-17,HIF-1,Toll-like receptor and Th17 cell differentiation.

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P<0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.

Objective To analyze the clinical characteristics,drug resistance and risk factors for poor prognosis in children patients with carbapenem resistant Klebsiella pneumoniae(CRKP)infection.Methods The samples of CRKP isolated from the children inpatients in this hospital from August 5,2016 to December 31,2020 were collected.The clinical data and drug resistance of CRKP in the patients with CRKP positive were analyzed.The risk factors in the poor prognosis group and good prognosis group of children pa-tients with CRKP infection conducted the correlation analysis.Results A total of 106 strains of non-repeti-tive CRKP were collected,which were mainly isolated from the patients ≤ 1 year old.The department distri-bution was dominated by the neonatal ICU and comprehensive ICU.CRKP showed the high resistance to mul-tiple antibacterial drugs,and its resistance rates to amikacin,levofloxacin,gentamicin,ciprofloxacin,minocy-cline and chloramphenicol were less than 30％.The poor prognosis rate in the children patients with CRKP in-fection reached 27.4％.The logistic multivariate regression analysis results showed that the multiple organ dysfunction and anemia were the independent risk factors for poor prognosis in the children patients with CRKP infection(P＜0.05).Conclusion The children CRKP infection is mainly the infants ≤1 years old,and CRKP shows the high resistance to multiple antibacterial drugs,the independent risk factors of poor prognosis include the multiple organ dysfunction and anemia

Objective To establish the rapid identification method of Hedysari Radix wild and cultivated products by integrating the identification characteristics of TCM traits obtained by intelligent senses such as electronic nose and colorimeter based on the multivariate statistical analysis method;To provide new ideas and methods for the formulation of commodity specification standards and the application research of market quality control for Hedysari Radix.Methods Totally 29 batches of samples of Hedysari Radix were detected based on colorimeter and electronic nose technology to obtain their sensory information,and the effective components of Hedysari Radix were determined by high performance liquid chromatography(HPLC)and other methods for joint analysis.After establishing the optimal experimental conditions of Hedysari Radix electronic nose,multivariate statistical analysis methods,such as principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA)and clustering analysis,were used to establish the identification model of Hedysari Radix wild and cultivated commodities.Results The optimum test conditions of Hedysari Radix electronic nose(particle size of 65 mesh):the sample weight was 2.0 g,the optimum temperature of the sample was 50℃,and the time was 25 min.A single intelligent sensory result could not quickly and accurately identify the two,but the fusion information could quickly identify the wild and cultivated commodities of Hedysari Radix,and the chemical composition had a certain correlation with the color and taste.Conclusion Electronic nose and colorimeter can quickly and accurately distinguish wild and cultivated Hedysari Radix after multivariate statistical analysis,which is simple and feasible.The combined analysis of its related properties and active components can be used for the quality evaluation of Hedysari Radix.

Objective To explore the alterations in gray matter volume(GMV)in adolescents with bipolar disorder(BD).Methods 36 BD patients(BD group)and 37 healthy controls(HC group)who underwent magnetic resonance imaging(MRI)for artificial visual inspection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University from September 2019 to December 2021 were selected.Structural MRI data were processed by using FreeSurferv6.0.0,and statistical analysis were conducted by using SPSS 26.0 and R language software.Receiver operating characteristic(ROC)curve were employed to assess the diagnostic efficacy of various brain regions.Results Compared to HC group,patients in BD group exhibited significant reductions in GMV in the right superior frontal gyrus,right nucleus accumbens,left insula,right lateral orbitofrontal cortex,and right medial orbitofrontal cortex(P＜0.05).ROC curve analysis indicated that area under the curve(AUC)for the right superior frontal gyrus and right nucleus accumbens were 0.739 and 0.712 respectively,while the combined AUC for multiple brain regions was 0.820.Conclusion Adolescents with BD show significant reductions in GMV in specific brain regions,provide reference for the early identification and pathological mechanism research of BD.

Objective To investigate the application value of extracellular volume fraction(ECV)obtained from enhanced CT in diagnosis and classification of acute pancreatitis.Methods The clinical data from patients with acute pancreatitis(acute pancreatitis group)and normal controls(control group)underwent enhanced CT were analyzed retrospectively.The CT values of pancreas and abdominal aorta in the same sclice on precontrast and equilibrium-phase images were measured,and then pancreatic ECV was calcu-lated.The measured parameters were compared between the groups of control and acute pancreatitis,and subgroups of non-severe and severe pancreatitis.The logistic regression analysis was used to identify the risk factors for acute pancreatitis and severe pancrea-titis,and the receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency in diagnosis and classifica-tion of acute pancreatitis.Results The pancreatic CT value and ECV were independent risk factors for acute pancreatitis(P＜0.05),and the ECV was an independent risk factor for severe pancreatitis(P＜0.05).The area under the curve(AUC)of ECV was higher in acute pancreatitis group(0.81)and severe pancreatitis subgroup(0.68).Conclusion As a quantitative parameter,the ECV obtained from enhanced CT has higher clinical application value and higher popularity in the diagnosis and classification of acute pancreatitis.

Anxiety is a major mood disorder, and the high morbidity, co-morbidity and disability of anxiety disorders seriously affect people's quality of life, so the importance and urgency of research on anxiety cannot be overstated. Animal models are the main carriers for studying the mechanism of disease occurrence and development, drug efficacy evaluation and drug development.Unconditioned anxiety model is a common anxiety model.Elevated plus maze test, open field test and light-dark box test are widely accepted paradigms for the detection of unconditioned anxiety.This kind of behavioral paradigm based on environmental exposure takes advantage of the conflict between curiosity and fear of the unfamiliar environment to simulate and detect the anxiety of animals.However, the validity of these behavioral paradigms for evaluating anxiety in animals is questionable.In this paper, we discuss the concept of anxiety, the definition of anxiety behavior in the behavioral test of unconditioned anxiety, and the factors to be considered in the test of unconditioned anxiety behavior.On this basis, new solutions were proposed to the contradictions and blind spots in order to improve the test paradigm of anxiety behavior and provide a more reliable animal model for the evaluation of anxiety.This paper presents a new approach to address the contradictions and blind spots of this paradigm.

Non-suicidal self-injury(NSSI)is a behavior that occurs most often in adolescents.Previous studies showed that this behavior has the addictive related characteristics.Interestingly,the addictive nature of NSSI behavior can be assessed using Ottawa selfinjury inventory(OSI),the higher addiction score indicates the more serious NSSI behavior.From the psychological mechanism,different models show that the addictive feature of NSSI behavior may be related to the behavioral reinforcement mechanism and the interaction mechanism of emotion,cognition,and behavior of susceptible individuals.From the neurobiological mechanisms,opioid and dopamine may mediate the addiction characteristics of NSSI,and the brain reward circuit originated in the midbrain system may play a key role.From the perspective of treatment,current psychotherapy may have advantages in alleviating NSSI behavior,while therapeutic drugs and non-invasive neural regulation of substance use disorders may improve NSSI behavior via alleviating behavioral addiction.In conclusion,NSSI may be an addictive disorder,which needs further verification in the future studies.