Exploring Importance and Regulation of Autophagy in Cancer Stem Cells and Stem Cell-Based Therapies.

Autophagy is a globally conserved cellular activity that plays a critical role in maintaining cellular homeostasis through the breakdown and recycling of cellular constituents. In recent years, there has been much emphasis given to its complex role in cancer stem cells (CSCs) and stem cell treatment. This study examines the molecular processes that support autophagy and how it is regulated in the context of CSCs and stem cell treatment. Although autophagy plays a dual role in the management of CSCs, affecting their removal as well as their maintenance, the intricate interaction between the several signaling channels that control cellular survival and death as part of the molecular mechanism of autophagy has not been well elucidated. Given that CSCs have a role in the development, progression, and resistance to treatment of tumors, it is imperative to comprehend their biological activities. CSCs are important for cancer biology because they also show a tissue regeneration model that helps with organoid regeneration. In other words, the manipulation of autophagy is a viable therapeutic approach in the treatment of cancer and stem cell therapy. Both synthetic and natural substances that target autophagy pathways have demonstrated promise in improving stem cell-based therapies and eliminating CSCs. Nevertheless, there are difficulties associated with the limitations of autophagy in CSC regulation, including resistance mechanisms and off-target effects. Thus, the regulation of autophagy offers a versatile strategy for focusing on CSCs and enhancing the results of stem cell therapy. Therefore, understanding the complex interactions between autophagy and CSC biology would be essential for creating therapeutic treatments that work in both regenerative medicine and cancer treatment.

Study protocol for a prospective, double-blinded, observational study investigating the diagnostic accuracy of an app-based diagnostic health care application in an emergency room setting: the eRadaR trial.

INTRODUCTION: Occurrence of inaccurate or delayed diagnoses is a significant concern in patient care, particularly in emergency medicine, where decision making is often constrained by high throughput and inaccurate admission diagnoses. Artificial intelligence-based diagnostic decision support system have been developed to enhance clinical performance by suggesting differential diagnoses to a given case, based on an integrated medical knowledge base and machine learning techniques. The purpose of the study is to evaluate the diagnostic accuracy of Ada, an app-based diagnostic tool and the impact on patient outcome. METHODS AND ANALYSIS: The eRadaR trial is a prospective, double-blinded study with patients presenting to the emergency room (ER) with abdominal pain. At initial contact in the ER, a structured interview will be performed using the Ada-App and both, patients and attending physicians, will be blinded to the proposed diagnosis lists until trial completion. Throughout the study, clinical data relating to diagnostic findings and types of therapy will be obtained and the follow-up until day 90 will comprise occurrence of complications and overall survival of patients. The primary efficacy of the trial is defined by the percentage of correct diagnoses suggested by Ada compared with the final discharge diagnosis. Further, accuracy and timing of diagnosis will be compared with decision making of classical doctor-patient interaction. Secondary objectives are complications, length of hospital stay and overall survival. ETHICS AND DISSEMINATION: Ethical approval was received by the independent ethics committee (IEC) of the Goethe-University Frankfurt on 9 April 2020 including the patient information material and informed consent form. All protocol amendments must be reported to and adapted by the IEC. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings. TRIAL REGISTRATION NUMBER: DRKS00019098.

Ethnobotanical study and phytochemical profiling of Heptapleurum hypoleucum leaf extract and evaluation of its antimicrobial activities against diarrhea-causing bacteria.

BACKGROUND: Due to the development of superbugs as a result of unprescribed and frequent use of antibiotics in recent years, an alternate form of medicine had to be introduced. In light of this global threat, researchers all over the world have been gravitating towards herbal medicines. In order to find out new ways of saving the planet using medicinal plants, ethnobotanical studies must be carried out. Concerning this, an ethnobotanical study has been done in this paper to identify potential medicinal plants in Rangamati, Bangladesh. RESULTS: For the ethnobotanical survey, randomized 104 people were interviewed and 62 different plant species were found to treat 19 different kinds of diseases and 84% of people reported to be completely recovered. Furthermore, among the 19 diseases found, the majority of them were common cold, abdominal pain or gastric, diarrhea, and dysentery. From the 62 different plant species, Heptapleurum hypoleucum, used for the treatment of diarrhea, was selected for conducting further studies due to its heavy use as reported by the tribal people. In this study, the aqueous, ethanol, and methanol extracts of Heptapleurum hypoleucum were subjected to microbial susceptibility assays using the agar well diffusion method. The test microorganisms were Salmonella typhi, Streptococcus pneumoniae, Staphylococcus aureus, Shigella flexneri, and Escherichia coli. Among these, the most susceptible organisms were Staphylococcus aureus (21 mm) and Salmonella typhi (19 mm) in the ethanolic extract. Also, the methanolic extract showed an inhibition zone of 13 mm against E. coli, which was more than that of the antibiotic's (11 mm). Phytochemical screening of the plant revealed that it contains alkaloids, phenols, steroids, and flavonoids, but lacks saponins and tannins. CONCLUSION: To combat the rising threat of antibiotic resistance, ethnoscience needs to be consolidated with modern biotechnological techniques to make the most use of the vast amount of natural resources. The findings of this study indicate that Heptapleurum hypoleucum, an ethnobotanical medicinal plant, has shown comparable antimicrobial activity with commercial antibiotics against several diarrhea-causing pathogens and also contains several medically important phytochemicals.

An Immunopharmacoinformatics Approach in Development of Vaccine and Drug Candidates for West Nile Virus.

An outbreak of West Nile Virus (WNV) like the recent Ebola can be more epidemic and fatal to public health throughout the world. WNV possesses utmost threat as no vaccine or drug is currently available for its treatment except mosquito control. The current study applied the combined approach of immunoinformatics and pharmacoinformatics to design potential epitope-based vaccines and drug candidates against WNV. By analyzing the whole proteome of 2994 proteins, the WNV envelope glycoprotein was selected as a therapeutic target based on its highest antigenicity. After proper assessment "KSFLVHREW" and "ITPSAPSYT" were found to be the most potential T and B-cell epitopes, respectively. Besides, we have designed and validated four novel drugs from a known WNV inhibitor, AP30451 by adopting computational approaches. Toxicity assessment and drug score confirmed the effectiveness of these drug candidates. This in silico research might greatly facilitate the wet lab experiments to develop vaccine and drug against WNV.

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments.

Formulation development of a cream containing fennel extract: in vivo evaluation for anti-aging effects.

This study was aimed to formulate and evaluate anti-aging effects of a topical cream (w/o emulsion) containig extract of Fennel (Foeniculum vulgare) versus its base. Formulation containing 4% concentrated extract of Foeniculum vulgare was developed by entrapping in the inner aqueous phase of w/o emulsion and base contained no extract. Both the base and formulation were stored under different storage conditions to predict their stability. The formulation and base were evaluated for effect on skin moisture and transepidermal water loss (TEWL). The base showed insignificant while the formulation showed significant effects on skin moisture and TEWL. The parameter volume and surface evaluation of living skin (SELS) parameters SEr, SEsc, SEsm, SEw were also evaluated and showed a significant (p < or = 0.05) decline. The texture parameter energy showed a significant increase proving that the formulation possesses potential anti-aging effects.

Antimicrobial activity of seed extracts and bondenolide from Caesalpinia bonduc (L.) Roxb.

The antibacterial and antifungal activities, along with a phytotoxicity test of the newly isolated diterpene bondenolide (1), of a methanol extract, ethylacetate fraction and water soluble part of the methanol extract of Caesalpinia bonduc (L.) Roxb. were assayed.

Chemical constituents from Asparagus dumosus.

The isolation and characterization of calonysterone (1), blechnoside B (2), 20-hydroxyecdysone and isovanillin from the whole plant of Asparagus dumosus are being reported for the first time from this source.

Steroidal saponins from Asparagus dumosus.

A new steroidal saponin, dumoside, characterized as (20S)-3 beta, 16 beta-dihydroxy pregn-5-ene-22-carboxylic acid (22, 16)-lactone-3-O-beta-chacotrioside, was isolated from the whole plant of Asparagus dumosus Baker and the structure was deduced from spectral data. In addition to dumoside three more steroidal saponins characterized as 3 beta-dihydroxy pregn-5,16-dien-20-one 3-O-beta-chacotrioside, 3 beta, 22 alpha, 26-trihydroxyfurost-5-ene-3-O-beta-chacotrioside-26-O- beta-D-glucopyranoside and its corresponding 22 alpha-O methoxy analogue were also isolated for the first time from this source. The structures have been identified with the help of FAB-MS, 1H NMR, 13C NMR and extensive 2D NMR spectroscopy, as well as comparison with reported spectroscopic data.