Alternative treatment of recurrent Clostridioides difficile infection in adults by fecal transplantation: an overview of phase I–IV studies from Clinicaltrials.gov

BackgroundFecal microbiota transplantation (FMT) is an interventional approach to treat chronic and recurrent Clostridioides difficile infection (CDI). However, there is insufficient evidence regarding its effectiveness and safety. Clinical trials have been conducted to inspect the safety and effectiveness of FMT with and without comparison to pharmacological treatments.AimThis review explored the treatment of CDI in adults using FMT and evaluated the safety of this intervention based on phase I–IV studies registered on Clinicaltrials.gov.MethodA comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated CDI in adults. Data on study type, study design, sample size, intervention details, and outcomes related to FMT were examined and evaluated.ResultsIn total, 13 clinical trials on FMT for CDI published through 17 November 2023 were identified, all of which were interventional studies. The investigation focused on both terminated and completed studies. Basic and advanced outcome measures were examined.ConclusionSome studies were terminated during phase II, and FMT was less effective than antibiotics such as vancomycin and fidaxomicin. However, colonoscopy and oral FMT were explored in several completed studies with promising results, but the evidence remains limited and inconclusive

Dose Optimization of Colistin: A Systematic Review

Colistin is considered a last treatment option for multi-drug and extensively resistant Gram-negative infections. We aimed to assess the available data on the dosing strategy of colistin. A systematic review was performed to identify all published studies on the dose optimization of colistin. Grey literature and electronic databases were searched. Data were collected in a specified form and the quality of the included articles was then assessed using the Newcastle-Ottawa scale for cohort studies, the Cochrane bias tool for randomized clinical trials (RCT), and the Joanna Briggs Institute (JBI) critical checklist for case reports. A total of 19 studies were included, of which 16 were cohort studies, one was a RCT, and two were case reports. A total of 18 studies proposed a dosing regimen for adults, while only one study proposed a dosing schedule for pediatric populations. As per the available evidence, a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h was considered the most appropriate dosing strategy to optimize the safety and efficacy of treatment and improve clinical outcomes. This review supports the administration of a loading dose followed by a maintenance dose of colistin in severe and life-threatening multi-drug Gram-negative bacterial infections

Dose optimization of β-lactams antibiotics in pediatrics and adults:A systematic review

Background: β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients

Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: “vancomycin”, “safety”, “efficacy” and “loading dose” combined with the Boolean operator “AND” or “OR”. Results: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. Conclusions: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions

The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule : targeting cancer cells signaling PI3K and AKT kinase pathway

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.BACKGROUND : Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage. METHODS : The current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through in silico analysis. RESULTS : The result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of −7.5, −7.9, and −7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound’s absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski’s rule of five. CONCLUSIONS : The finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.Princess Nourah bint Abdulrahman University Researchers Supporting Project.https://www.frontiersin.org/journals/oncologyMedical OncologySDG-03:Good heatlh and well-bein

Phenetic and cladistic analyses of Boraginaceae Juss.

Abstract Background The systematics of family Boraginaceae draw attention of many botanists for many years. The current study's primary goals are to clarify phenetic and phylogenetic relationships within Boraginaceae according to morphology and molecular characteristics and to evaluate the morphological characters that can be applied in systematics of Boraginaceae. Results The macromorphological characters of 39 species, 2 subspecies and 5 varieties of wild boraginaceous plants were extracted and subjected to phenetic and principal component analysis that was performed for detecting the most important characters differentiating the studied taxa. The generated dendrogram is divided into five clear groups; Arnebia decumbens var. macrocalyx and Heliotropium curassavicum are the most distantly related species, while Echium angustifolium subsp. angustifolium and E. angustifolium subsp. sericeum are the most closely related species. The phylogenetic relations among the examined taxa were determined using DNA barcoding of the rbcl gene. The phylogenetic analysis generated a cladogram showing that among the studied taxa of Boraginaceae there is a bolster for three clear lineages with resolved relationships. Conclusions It is concluded that the chosen morphological characters were important in species delimitation, where more than half of the total morphological variations (67.94%) were explained by the first two principal components, indicating that the morphological characters showed high variability, which is useful for discrimination, and these characters, in addition to molecular characters, shared in drawing the phenetic and phylogenetic relationships within Boraginaceae that were considered not monophyletic groups. Boraginaceae contained some monophyletic genera such as Heliotropium and Alkanna, while the other studied taxa expressed a non-monophyletic relationships

In Vitro Anticancer and Antibacterial Activities of the Essential Oil of Forsskal's Basil Growing in Extreme Environmental Conditions

Many species belonging to the genus Ocimum are used for aromatic, medicinal, and cosmetic purposes. The essential oil (OFEO) obtained by hydrodistillation of the flowering aerial parts of Forsskal's Basil "Ocimum forskolei Benth" growing in extreme environmental conditions in Mecca Region, Saudi Arabia was analyzed by GC-MS. The main constituents were phenylpropanoids (methyl eugenol 55.65% and eugenol 11.66%), monoterpene (linalool 9.75%), and sesquiterpenes (germacrene D 3.72% and beta-caryophyllene 2.57%). The OFEO was tested against MCF7, HT29, and HCT116 cancer cells and compared with normal fibroblast cells (MRC5). The MTT assay showed that HCT116 was more sensitive to OFEO (IC50 5.34 mu g/mL), which reduced the number of HCT116 colonies at 6 mu g/mL, while causing complete colony death at 12 and 24 mu g/mL. Western Blotting and qRT-PCR were used to evaluate the level change of different proteins with respect to GAPDH. OFEO upregulated the apoptotic protein (caspase 3), and downregulated the cell proliferation proteins (AKT and pAKT), cell cycle arrest (PCNA, Cyclin D1), and the anti-apoptotic Bcl2 proteins. OFEO was also tested against reference strains of Gram-negative and Gram-positive bacteria including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus by using the well-diffusion and assessing their MICs, which ranged from 250 to 500 mu g/mL

Table_1_The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule: Targeting cancer cells signaling PI3K and AKT kinase pathway.doc

BackgroundBreast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage.MethodsThe current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through in silico analysis.ResultsThe result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of −7.5, −7.9, and −7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound’s absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski’s rule of five.ConclusionsThe finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.</p