Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using MOE (Molecular Operating Environment), we performed molecular docking studies on these drugs binding to a range of targets including ribosome targets in Leishmania and H. sapiens. Our study shows that the two drugs do not bind to the same pockets in Leishmania targets but to the same pockets in the human ribosome, with some differences in interactions. Moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.
Todd A. YoungMatthew George Jr.Ayele GugssaWilliam M. SoutherlandYayin FangClarence M. Lee
Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.
Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.
Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uter
Ummi Shahieda Lazaroo Bt Zurrein Shah LazarooNavanithan SivanananthanChua Kia How
In this work,we sought to investigate constrained docking control during shipborne SideArm recovery of an Unmanned Aerial Vehicle(UAV)under preassigned safe docking constraints,rough ocean environments,and different initial positions.The aim was to solve the UAV tracking-lag problem that manifests when attempting to dock with a rapidly moving SideArm and to improve the accuracy and rapidity of docking.First,together with the formulations of the shipborne SideArm system and environmental airflows,the affine nonlinear dynamics of the hook was established to reduce tracking lag.Then,echo state network approximators with good approximation capacity and low computational consumption were designed to accurately approximate the UAV’s unknown nonlinear dynamics.With feedforward compensation provided by these approximators,a nonlinear-mapping-based constrained docking control law was developed for shipborne SideArm recovery of UAVs.This approach to controlling the docking trajectory and the forward docking speed of the UAV can achieve rapid and exact docking with a moving SideArm,without violating the preassigned safe docking-constraint envelopes.Simulations under different docking scenarios were used to validate the effectiveness and advantages of the proposed docking-control algorithm.
Zikang SUZhuolin XINGXuebing LIChuntao LIXinwei WANGHonglun WANG
Hispidin is a pyranone compound found in edible and medicinal mushrooms of the Phellinus and Inonotus genera.This investigation used fluorescence spectroscopy,UV absorption spectroscopy,and molecular docking to examine the interaction of hispidin with pepsin.The Stern-Volmer method was used to perform the fluorescence quenching measurements at different temperatures(298 K,303 K,and 310 K).According to the findings,hispidin induced a static quenching mechanism in pepsin that resulted in the creation of a hispidin-pepsin complex with binding constants(Ka)ranging from 9.56×10^(4) to 3.45×10^(5) L mol^(-1).The positive values ofΔH(84.6 kJ mol-1)andΔS(337.9 J mol^(-1) K^(-1))demonstrated that hydrophobic forces contributed to forming the hispidin-pepsin complex.The findings of UV-vis absorption,synchronous fluorescence,and 3D fluorescence spectraspectra demonstrated that hispidin altered the conformation and microenvironment of pepsin.According to the analysis of molecular docking,hispidin got into the pepsin's active cavity.The research clarifies the molecular mechanisms by which hispidin binds to pepsin and helps understand its possible biological activity in vivo.
Unmanned autonomous Air-to-Air Refueling(AAR)capability is the key guarantee to support the distant-field,high-intensity and durable operations of the penetration counterair combat system.In the future,the long-range unmanned reconnaissance and attack platform can reach the maximum flight range requirement through AAR.At present,large transport aircraft platforms in China are still equipped with probe-and-drogue systems,and the refueling mode is gradually changing from manned to unmanned autonomous operation.The docking process is the riskiest and most important part,and there are strict safety,precision,and efficiency requirements for refueling operation,especially during close-distance docking and formation maintenance phases.In this paper,five issues that need to be solved to achieve autonomous AAR docking are summarized.On this basis,five key technology development needs are proposed to solve these engineering issues.Finally,some prospects are given.
Aromatic hydrocarbons generally refer to compounds containing benzene rings.Many types of isomers can be formed by replacing hydrogen atoms on the benzene ring.In this paper,an aromatic-hydrocarbon-inspired modular robot(AHIMR)is proposed.The robot can be reassembled into different configurations suitable for various task requirements.A vision-based docking system is designed for the AHIMR.The system primarily consists of two stages:a remote guidance stage and a precise docking stage.During the remote guidance stage,an object module is identified using an illumination adaptive target recognition algorithm,and then the active module moves to the docking area through communication with ZigBee.In the precise docking stage,the active module calculates the relative pose with the object module using a perspective-n-point method and dynamically adjusts its posture to dock.In this process,a Kalman filter is used to reduce target occlusion and jitter interference.In addition,the docking system feasibility is verified via several simulation experiments.The module docking accuracy is controlled within 0.01 m,which meets the reconfiguration task requirements of the AHIMR.In the AHIMR submodule docking experiment,the active module accurately moves to the expected position with a docking success rate of 95%.