Recent advances in anti-infective drug discovery最新文献

Background: Endometriosis is one of the common diseases of women, especially in reproductive age, and it is one of the most important causes of infertility in women. The aim of this study was to investigate the level of mRNA-TLR-5 expression in women with endometriosis.

Methods: The present study was performed in Nikan Hospital, Tehran, Iran, in 2021. The samples of endometrial mucosa for the eutopic group and an ovarian endometriotic cyst for the ectopic group were obtained from the patients who underwent laparoscopic surgery at the Fetal Infertility Center and were diagnosed with endometriosis. Normal endometrial samples were also obtained from patients who had no history of infertility and underwent laparoscopic TL surgery for reasons other than endometriosis such as ovarian cysts (control group). After RNA extraction and cDNA synthesis, TLR-5 gene expression was evaluated by the Real-Time PCR method.

Results: Based on the results of the comparison of TLR-5 gene expression in all three ectopic, eutopic endometrium, and control groups by Real-Time PCR, it was found that the TLR-5 gene expression is significantly higher in ectopic samples than in the other two groups, but there is a significant difference between two utopic and control groups.

Conclusion: The increase in TLR-5 expression in the ectopic group can probably be a reason for reducing the apoptosis of cells entered into the peritoneal cavity and creating an environment for the survival and proliferation of these cells.

Background: Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and lifethreatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection.

Objective: The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects.

Methods: SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex vivo permeation study, in vitro and in vivo antibacterial activity were conducted.

Results: The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5.03 ± 0.15 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel.

Conclusion: Ex vivo studies ascertain the presence of the drug at the desired site and improve therapy. In vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

Background: The pleiotropic effect of cholecalciferol (vitamin D₃) has gained significant momentum and has been explored widely.

Objectives: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli.

Methods: An in vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method.

Results: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli.

Conclusion: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

Introduction: Hyperpyrexia, algesia and inflammation are pathological disorders which are treated with synthetic as well as herbal medications.

Aims: The basic aim of the present study is to evaluate the ethnopharmacological activities of phytoconstituents that are present in C. colocynthis (fruit extract) by using in vivo and in silico studies.

Methods: Thirty-six albino rats were used in our studies with an average weight between 150-170 g. Anti-inflammatory activity was investigated using carrageenan (an extract from a red seaweed) that induced edema in albino rat paws. However, in antipyretic and analgesic activity studies, yeast and acetic acid were used to cause pyrexia or algesia, respectively. Different doses of acetone fruit extract were used to treat inflammation, pyrexia and algesia.

Results: Our results showed that the maximum percentage inhibition of acetonic fruit extract in anti-inflammatory and analgesic activities was observed at 70% and 100%, respectively, with 400 mg/kg doses, and in pyretic activity the maximum inhibitory percentage was 86% with a 100 mg/kg dose. In in silico analysis, we have shown that bioactive compounds (α-spinasterol, ascorbic acid and chlorogenic acid) found in fruit extract have outstanding inhibition properties that involves proteins PTGS2, TLR2 and TRPV4. C. colocynthis fruit extract shows results that are statistically significant (p < 0.005) and comparable to a reference drug. Acetonic fruit extract of C. colocynthis can be used as a natural and safe remedy with no side effects.

Conclusion: Both in vivo and in silico studies on chlorogenic acid, ascorbic acid and α-spinasterol have shown that these are inhibitory compounds that can be used for boosting the immune response.

Background: Plants are harmed by parasitic organisms, and toxic poisons are created. Phytopathogenic fungi create toxins that can severely harm plants' basic physiological functioning.

Objective: Investigation of antifungal impact of various fractions of methanol extract of Artemisia herba-alba to Aspergillus niger as a plant pathogen.

Methods: Artemisia herba-alba extract was purified using column chromatography, giving various antifungal fractions tested versus A. niger.

Results: The 6^th fraction give the highest inhibition zone with a diameter of 5.4 cm and MIC 125.02 ± 4.9 μg/ml, which was identified using Mass spectroscopy, ¹HNMR, Elemental analysis as well as IR testing, revealing the chemical formula of the purified fraction. Ultrastructure alteration of treated A. niger was examined versus control using the transmission electron microscope. Purified fraction has tested versus normal cell line with minimal cytotoxicity.

Conclusion: These results revealed the possibility of using Artemisia herba-alba methanol extract as a promising antifungal versus phytopathogenic fungi, especially A. niger after more verification of results.

Background: Ebola virus (EBOV) is a genus of negative-strand RNA viruses belonging to the family Filoviradae that was first described in 1976 in the present-day Democratic Republic of the Congo. It has intermittently affected substantial human populations in West Africa and presents itself as a global health menace due to the high mortality rate of patients, high transmission rate, difficult patient management, and the emergence of complicated autoimmune disease-like conditions post-infection.

Objective: EBOV or other EBOV-like species as a biochemical weapon pose a significant risk; hence, the need to develop both prophylactic and therapeutic medications to combat the virus is unquestionable.

Methods: In this review work, we have compiled the literature pertaining to transmission, pathogenesis, immune response, and diagnosis of EBOV infection. We included detailed structural details of EBOV along with all the available therapeutics against EBOV disease. We have also highlighted current developments and recent advances in therapeutic approaches against Ebola virus disease (EVD).

Discussion: The development of preventive vaccines against the virus is proving to be a successful effort as of now; however, problems concerning logistics, product stability, multi- dosing, and patient tracking are prominent in West Africa. Monoclonal antibodies that target EBOV proteins have also been developed and approved in the clinic; however, no small drug molecules that target these viral proteins have cleared clinical trials. An understanding of clinically approved vaccines and their shortcomings also serves an important purpose for researchers in vaccine design in choosing the right vector, antigen, and particular physicochemical properties that are critical for the vaccine's success against the virus across the world.

Conclusion: Our work brings together a comprehensive review of all available prophylactic and therapeutic medications developed and under development against the EBOV, which will serve as a guide for researchers in pursuing the most promising drug discovery strategies against the EBOV and also explore novel mechanisms of fighting against EBOV infection.

Background: The most significant sexually transmissible fungal disease, semen candidiasis, is caused by Candida albicans and impacts male reproductive potential. Actinomycetes are a group of microorganisms that could be isolated from various habitats and used for the biosynthesis of various nanoparticles with biomedical applications.

Objective: Testing antifungal activity of biosynthesized Ag nanoparticles versus isolated C. albicans from semen as well as its anticancer activity versus the Caco-2 cell line.

Methods: Screening 17 isolated actinomycetes for the biosynthesis of Ag nanoparticle biosynthesis. Characterization of biosynthesized nanoparticles, testing its anti-Candida albicans, and antitumor activity.

Results: Streptomyces griseus was the isolate that identified silver nanoparticles using UV, FTIR, XRD and TEM. Biosynthesized nanoparticles have promising anti-Candida albicans with MIC (125 ± 0.8) µg/ml and accelerate apoptotic rate versus Caco-2 cells (IC50 = 7.30 ± 0.54 µg/ml) with minimal toxicity (CC50 = 142.74 ± 4.71 µg/ml) versus Vero cells.

Conclusion: Certain actinomycetes could be used for the biosynthesis of nanoparticles with successive antifungal and anticancer activity to be verified by in vivo studies.