RESUMO
BACKGROUND: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. CONCLUSIONS: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Endostatinas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Endostatinas/administração & dosagem , Endostatinas/uso terapêutico , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Adulto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Channel-regulated peptides (CRPs) derived from animal venom hold great promise as potential drug candidates for numerous diseases associated with channel proteins. However, discovering and identifying CRPs using traditional bio-experimental methods is a time-consuming and laborious process. While there were a few computational studies on CRPs, they were limited to specific channel proteins, relied heavily on complex feature engineering, and lacked the incorporation of multi-source information. To address these problems, we proposed a novel deep learning model, called DeepCRPs, based on graph neural networks for systematically mining CRPs from animal venom. By combining the sequence semantic and structural information, the classification performance of four CRPs was significantly enhanced, reaching an accuracy of 0.92. This performance surpassed baseline models with accuracies ranging from 0.77 to 0.89. Furthermore, we employed advanced interpretable techniques to explore sequence and structural determinants relevant to the classification of CRPs, yielding potentially valuable bio-function interpretations. Comprehensive experimental results demonstrated the precision and interpretive capability of DeepCRPs, making it an accurate and bio-explainable suit for the identification and categorization of CRPs. Our research will contribute to the discovery and development of toxin peptides targeting channel proteins. The source data and code are freely available at https://github.com/liyigerry/DeepCRPs.
Assuntos
Semântica , Peçonhas , Animais , Peptídeos , Redes Neurais de ComputaçãoRESUMO
The spiders Psechrus triangulus and Hippasa lycosina are widely distributed in Yunnan Province, China, and are important natural enemies of agricultural pests, yet studies regarding the composition of their venom are lacking. In this study, cDNA libraries were constructed from venom gland tissue of P. triangulus and H. lycosina and used for transcriptomic analysis. From the analysis, 39 and 31 toxin-like sequences were predicted for P. triangulus and H. lycosina, respectively. The predicted neurotoxin sequences were categorized according to cysteine sequence motifs, and the predicted neurotoxin sequences of P. triangulus and H. lycosina could be classified into 9 and 6 toxin families, respectively. In addition, potential acetylcholinesterase, hyaluronidase, and astaxanthin-like metalloproteinases were identified through annotation. In summary, transcriptomic techniques were invaluable in mining the gene expression information from these two spider species to explore the toxin composition of their venom and determine how they differ. Studies of this type provide essential baseline data for studying the evolution and physiological activities of spider toxins and for the potential development of medicinal compounds.
Assuntos
Venenos de Aranha , Transcriptoma , Animais , Neurotoxinas , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , China , Venenos de Aranha/genética , Venenos de Aranha/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.
Assuntos
Artrite Reumatoide , Ferroptose , Sinoviócitos , Vespas , Animais , Humanos , Venenos de Vespas/farmacologia , Venenos de Vespas/metabolismo , Venenos de Vespas/uso terapêutico , Interleucina-6/metabolismo , Vespas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proliferação de Células , Antioxidantes/farmacologia , Oxirredução , Fibroblastos , Luciferases , Lipídeos/farmacologia , Células CultivadasRESUMO
A new genus of the spider family Macrothelidae Simon, 1892, Vacrothele Tang Yang gen. nov. is described, along with two new species: V. pseudohunanica sp. nov., V. uncata sp. nov.. Three Macrothele species are transferred to the new genus: V. hunanica (Zhu Song, 2000) comb. nov., V. digitata (Chen Jiang, 2020) comb. nov., and V. palpator (Pocock, 1901) comb. nov..
Assuntos
Aranhas , Distribuição Animal , Estruturas Animais , Animais , ChinaRESUMO
During long-term predator-prey coevolution, spiders have generated a vast diversity of toxins. Trichonephila clavata is a web-spinning spider whose large, well-constructed webs and venomous arsenal facilitate prey capture. In contrast, Sinopoda pengi is an ambush predator with agile locomotion and strong chelicerae for hunting. In this study, transcriptomic analysis was performed to describe the predicted toxins of S. pengi and T. clavata. A total of 43 and 47 of these unigenes from S. pengi and T. clavata, respectively, were predicted to have toxin activity. Putative neurotoxins were classified to the family level according to cysteine arrangement; 4 and 6 toxin families were produced by S. pengi and T. clavata, respectively. In addition, potential metalloproteases, acetylcholinesterases, serine proteases, hyaluronidases and phospholipases were found by annotation in databases. In summary, molecular templates with potential application value for medical and biological fields were obtained by classifying and characterizing presumed venom components, which established a foundation for further study of venom.
Assuntos
Venenos de Aranha , Aranhas , Animais , Perfilação da Expressão Gênica , Neurotoxinas/genética , Venenos de Aranha/genética , Aranhas/genética , TranscriptomaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cybister chinensis Motschulsky belongs to the family Dytiscidae. As a traditional Chinese medicine, the insect is called Longshi in the folk and is commonly used to treat enuresis in children and frequent urination in the elderly. AIM OF THE STUDY: Inflammation is involved in chronic kidney disease. The previous study proved ethanol extract of C. chinensis exhibited anti-inflammation effects in the Doxorubicin-induced kidney disease. However, the material basis and their possible mechanism of the insect were still unclear. Thus, we aimed to separate the active compounds of the ethanol extract from C. chinensis and to investigate their possible mechanism of anti-inflammation by network pharmacology and molecular docking. MATERIALS AND METHODS: The insect was extracted with 75% ethanol to produce ethanol extracts and then were extracted by petroleum ether, ethyl acetate and n-butanol respectively. Silica gel column chromatography and preparative HPLC were applied to separate the compounds of the extract. The compounds were characterized and identified by NMR and mass. The compound associated genes were collected by BATMAN-TCM database and the inflammation associated genes were obtained through DigSee database. The protein-protein interaction (PPI) network was carried out via Search Tool for the Retrieval of Interacting Genes/Protein (STRING) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway analysis was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The possible mechanism of compounds against inflammation was investigated by molecular docking. Finally, the anti-inflammatory effect of the representative compound was verified by the LPS-induced Raw 264.7 cell inflammatory model. TNF-α, IL-1ß and IL-6 of the cell supernatants were analyzed via using ELISA kits and the key proteins in JAK2/STAT3 signaling pathway were verified via the Western blot assays. RESULTS: Among crude extracts from C. chinensis, ethyl acetate extract showed the obvious anti-inflammatory effects. Nine compounds were isolated from ethyl acetate extract of Cybister chinensis for the first time, including benzoic acid (1), hydroxytyrosol (2), protocatechualdehyde (3), N-[2-(4-hydroxyphenyl)ethyl]acetamide (4), (2E)-3-phenylprop-2-enoic acid (5), 3-phenylpropionic acid (6), methyl 3,4-dihydroxybenzoate (7), 1,4-diphenyl butane-2,3-diol (8) and p-N,N-dimethylaminobenzaldehyde (9). After searching in the database, 1079 compound associated genes and 467 inflammation associated genes were found. The 137 common targets covered 77 signaling pathways, in which HIF-1 signaling pathway, TNF signaling pathway, influenza A, PI3K/Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and Jak-STAT signaling pathway were important for inflammation. Molecular docking studies showed compound 1, 4, 5, 6, 7 and 8 were the potential inhibitors of JAK2 protein. In addition, the in vitro test showed compound 5 reduced the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, it was found that compound 5 inhibited the expression of p-JAK2 and p-STAT3 in LPS-induced RAW264.7 cells in a dose-dependent manner. CONCLUSIONS: Based on the network pharmacology and molecular docking, the study suggested that C. chinensis could relieve the inflammation based on the multi-compounds and multi-pathways, which provided the foundation for the medicinal application of C. chinensis.
Assuntos
Anti-Inflamatórios/farmacologia , Besouros , Inflamação/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Anti-Inflamatórios/química , Medicina Tradicional Chinesa , Camundongos , Células RAW 264.7 , Transdução de SinaisRESUMO
Two new species of the genus Pseudopoda Jäger, 2000 are reported from Yunnan Province, China: Pseudopoda mingshengi sp. nov. (male, female) and P. uncata sp. nov. (male, female). The male of P. physematosa Zhang, Jäger & Liu, 2019 is described for the first time.
Assuntos
Aranhas , Animais , Feminino , Masculino , ChinaRESUMO
PURPOSE: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. METHODS: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. RESULTS: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. CONCLUSIONS: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.
Assuntos
Colite Ulcerativa , Periplaneta , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Feminino , Mucosa Intestinal , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-DawleyRESUMO
Abstract Purpose: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. Methods: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. Results: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. Conclusions: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.
Assuntos
Animais , Masculino , Feminino , Ratos , Periplaneta , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Colo , Mucosa IntestinalRESUMO
This paper concerns four species of the spider genus Uroctea Dufour, 1820 (Oecobiidae) from China. Two species, U. compactilis L. Koch, 1878 and U. lesserti Schenkel, 1936 are redescribed. Two new species are described here under the names U. multiprocessa Yang Zhang sp. nov. (male only, from Batang County of Sichuan Prov.) and U. yunlingensis Yang Zhao sp. nov. (both sexes from Yunling Mountains area of Yunnan Prov.). Color images of habitus and genitalia, SEM images of the male palps, and illustrations of epigynes of all species are provided. Specimens examined are deposited in the Institute of Entomoceutics Research, Dali University, China (DUIER) and School of Life Sciences, Southwest University, China (SWUC).
Assuntos
Aranhas , Animais , China , Cor , Feminino , MasculinoRESUMO
As a folk medicine of the Jingpo minority in Yunnan province, the venom of Vespa magnifica has been commonly used for the treatment of rheumatoid arthritis. Quality standardization of the wasp venom is a necessary step for its pharmaceutical research and development. To control the quality of the wasp venom, a method based on high-performance liquid chromatography (HPLC) was developed for chemical fingerprint analysis. In the chromatographic fingerprinting, chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), and principal component analysis (PCA), were applied to classify 134 batches (S1-S134) of wasp venom from different origins. The HPLC fingerprint method displayed good precision (Relative standard deviation, RSD < 0.27%), stability (in 16 h, RSD < 0.34%), and repeatability (RSD < 1.00%). Simultaneously, four compounds (VMS1, VMS2, VMS3, and VMS4) in the wasp venom were purified and identified. VMS1 was 5-hydroxytryptamine, and the other compounds were three peptides that were sequenced as follows: Gly-Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg-Ile-Asp-NH2 (VMS2), Ile-Asn-Leu-Lys-Ala-Ile-Ala-Ala-Leu-Ala-Lys-Lys-Leu-Leu-NH2 (VMS3), and Phe-Leu-Pro-Ile-Ile-Gly-Lys-Leu-Leu-Ser-Gly-Leu-Leu-NH2 (VMS4). The quantifications for these components were 110.2 mg/g, 26.9 mg/g, 216.3 mg/g, and 58.0 mg/g, respectively. The results of this work indicated that the combination of the chemical fingerprint and quantitative analysis offers a reasonable way to evaluate the quality of wasp venom.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Peptídeos/isolamento & purificação , Serotonina/isolamento & purificação , Venenos de Vespas/química , Sequência de Aminoácidos , Animais , Anti-Inflamatórios/química , Artrite Reumatoide/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/normas , Humanos , Medicina Tradicional Chinesa , Medicina Tradicional/métodos , Mapeamento de Peptídeos/métodos , Peptídeos/química , Análise de Componente Principal , Controle de Qualidade , Serotonina/química , VespasRESUMO
Four new species of Psechrus are described from Yunnan Province: P. changminae sp. nov., P. conicus sp. nov., P. discoideus sp. nov. and P. spatulatus sp. nov. Herewith the number of species belonging to Psechrus in Yunnan Province extended from five to nine. Illustrations and colour photos are provided, with comparison of intraspecific variation of copulatory organs.
Assuntos
Aranhas/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Estruturas Animais/crescimento & desenvolvimento , Animais , Tamanho Corporal , China , Feminino , Masculino , Tamanho do Órgão , Aranhas/anatomia & histologia , Aranhas/crescimento & desenvolvimentoRESUMO
This review describes the history of taxonomic research on scorpions and provides an updated checklist and key of the scorpions currently known in China. This checklist is based on a thorough review of the extant literatures on scorpion species whose presence has been confirmed in China through field expeditions and examination of scorpion collections, excepting a few members that have no clear distribution or are currently in doubt. Totally, the scorpion fauna of China consists of 53 species and subspecies belonging to 12 genera crossing five families, with 33 species (62.3%) and one genus being recorded as endemic. Additionally, identification key and the distribution of scorpions from China are provided.
Assuntos
Aracnídeos/classificação , Aracnídeos/fisiologia , Animais , China , DemografiaRESUMO
Psechrus kunmingensis Yin, Wang & Zhang, 1985 was first described from the female only. The first illustration of the male appeared without any text description and lacked other critical information. For this study, we collected fresh specimens of this species from diverse localities around Yunnan Province, China. Here, the male is described in detail for the first time and a supplementary description of the female is given. Based on the largest collection of Psechrus kunmingensis specimens ever assembled, we found a remarkably high level of morphological variation in this species.