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Frontiers in Bioscience (Landmark... Jun 2024The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the... (Review)
Review
The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the case with other chemotherapeutic agents, resistance development constrains their effectiveness. One putative mechanism of resistance is the promotion of autophagy, which is a direct consequence of the inhibition of the mTOR signaling pathway. Autophagy is primarily considered to be a cytoprotective survival mechanism, whereby cytoplasmic components are recycled to generate energy and metabolic intermediates. The autophagy induced by everolimus and temsirolimus appears to play a largely protective function, whereas a cytotoxic function appears to predominate in the case of rapamycin. In this review we provide an overview of the autophagy induced in response to mTOR inhibitors in different tumor models in an effort to determine whether autophagy targeting could be of clinical utility as adjuvant therapy in association with mTOR inhibition.
Topics: Humans; Autophagy; TOR Serine-Threonine Kinases; MTOR Inhibitors; Animals; Neoplasms; Signal Transduction; Antineoplastic Agents; Cytoprotection; Sirolimus
PubMed: 38940039
DOI: 10.31083/j.fbl2906231 -
BMC Infectious Diseases Jun 2024Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection.
METHODS
Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions.
RESULTS
Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period.
CONCLUSIONS
Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.
Topics: Humans; Helicobacter Infections; Male; Female; Helicobacter pylori; Middle Aged; Immunoglobulins; Adult; Anti-Bacterial Agents; Treatment Outcome; Aged; Drug Therapy, Combination; Clarithromycin; Amoxicillin; Young Adult; Antibodies, Bacterial
PubMed: 38937679
DOI: 10.1186/s12879-024-09498-4 -
Scientific Reports Jun 2024Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus...
Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus aureus and Staphylococci other than S. aureus (SOSA) among young volunteers in Egypt to determine their risk potential. Nasal swabs collected over 1 week in June 2019 from 196 volunteers were cultured for staphylococcus isolation. The participants were interviewed to assess sex, age, general health, hospitalization and personal hygiene habits. Identification was carried out using biochemical tests and VITEK 2 automated system. Disc diffusion and minimum inhibitory concentration tests were performed to determine antibiotic susceptibility. Screening for macrolide resistance genes (ermA, ermB, ermC, ermT and msrA) was performed using polymerase chain reaction. Thirty four S. aureus and 69 SOSA were obtained. Multi-drug resistance (MDR) was detected among most staphylococcal species, ranging from 30.77% among S. hominis to 50% among S. epidermidis. Phenotypic resistance to all tested antibiotics, except for linezolid, was observed. Susceptibility to rifampicin, vancomycin and teicoplanin was highest. ermB showed the highest prevalence among all species (79.41% and 94.2% among S. aureus and SOSA, respectively), and constitutive macrolide-lincosamide-streptogramin B (MLS) resistance was equally observed in S. aureus and SOSA (11.11% and 16.22%, respectively), whereas inducible MLS resistance was more often found in S. aureus (77.78% and 43.24%, respectively). The species or resistance level of the carried isolates were not significantly associated with previous hospitalization or underlying diseases. Although over all colonization and carriage of resistance genes are within normal ranges, the increased carriage of MDR S. aureus is alarming. Also, the fact that many macrolide resitance genes were detected should be a warning sign, particularly in case of MLS inducible phenotype. More in depth analysis using whole genome sequencing would give a better insight into the MDR staphylococci in the community in Egypt.
Topics: Humans; Egypt; Female; Male; Staphylococcus; Microbial Sensitivity Tests; Staphylococcal Infections; Anti-Bacterial Agents; Adult; Phenotype; Young Adult; Genotype; Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Adolescent
PubMed: 38937465
DOI: 10.1038/s41598-024-60924-8 -
PLoS Neglected Tropical Diseases Jun 2024Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds...
BACKGROUND
Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA.
METHODOLOGY
In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf.
PRINCIPAL FINDINGS
Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections.
CONCLUSIONS/SIGNIFICANCE
This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.
Topics: Elephantiasis, Filarial; Humans; Mass Drug Administration; Albendazole; Samoa; Diethylcarbamazine; Ivermectin; Male; Female; Adult; Filaricides; Middle Aged; Adolescent; Animals; Young Adult; Child; Prevalence; Antigens, Helminth; Drug Therapy, Combination; Child, Preschool; Wuchereria bancrofti; Aged
PubMed: 38935622
DOI: 10.1371/journal.pntd.0012236 -
The Pan African Medical Journal 2024Lymphatic filariasis is a neglected tropical disease that affects the lymphatic system of humans. The major etiologic agent is a nematode called Wuchereria bancrofti,... (Review)
Review Meta-Analysis
Lymphatic filariasis is a neglected tropical disease that affects the lymphatic system of humans. The major etiologic agent is a nematode called Wuchereria bancrofti, but Brugia malayi and Brugia timoriare sometimes encountered as causative agents. Mosquitoes are the vectors while humans the definitive hosts respectively. The burden of the disease is heavier in Nigeria than in other endemic countries in Africa. This occurs with increasing morbidity and mortality at different locations within the country, the World Health Organization recommended treatments for lymphatic filariasis include the use of Albendazole (400mg) twice per year in co-endemic areas with loa loa, Ivermectin (200mcg/kg) in combination with Albendazole (400mg) in areas that are co-endemic with onchocerciasis, ivermectin (200mcg/kg) with diethylcarbamazine citrate (DEC) (6mg/kg) and albendazole (400mg) in areas without onchocerciasis. This paper covered a systematic review, meta-analysis, and scoping review on lymphatic filariasis in the respective geopolitical zones within the country. The literature used was obtained through online search engines including PubMed and Google Scholar with the heading "lymphatic filariasis in the name of the state", Nigeria. This review revealed an overall prevalence of 11.18% with regional spread of Northwest (1.59%), North Central and North East, (4.52%), South West (1.26%), and South-South with South East (3.81%) prevalence. The disease has been successfully eliminated in Argungu local government areas (LGAs) of Kebbi State, Plateau, and Nasarawa States respectively. Most clinical manifestations (31.12%) include hydrocele, lymphedema, elephantiasis, hernia, and dermatitis. Night blood samples are appropriate for microfilaria investigation. Sustained MDAs, the right testing methods, early treatment of infected cases, and vector control are useful for the elimination of lymphatic filariasis for morbidity management and disability prevention in the country. Regional control strategies, improved quality monitoring of surveys and intervention programs with proper records of morbidity and disability requiring intervention are important approaches for the timely elimination of the disease in Nigeria.
Topics: Elephantiasis, Filarial; Humans; Nigeria; Animals; Wuchereria bancrofti; Filaricides; Albendazole; Neglected Diseases; Ivermectin; Brugia malayi
PubMed: 38933431
DOI: 10.11604/pamj.2024.47.142.39746 -
Pharmaceuticals (Basel, Switzerland) May 2024There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli...
There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by , which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections.
PubMed: 38931358
DOI: 10.3390/ph17060691 -
Microorganisms Jun 2024Waste Water Treatment Plants (WWTP) aim to reduce contamination in effluent water; however, studies indicate antimicrobial resistance genes (ARGs) persist...
Metagenomic Investigation of the Short-Term Temporal and Spatial Dynamics of the Bacterial Microbiome and the Resistome Downstream of a Wastewater Treatment Plant in the Iskar River in Bulgaria.
Waste Water Treatment Plants (WWTP) aim to reduce contamination in effluent water; however, studies indicate antimicrobial resistance genes (ARGs) persist post-treatment, potentially leading to their spread from human populated areas into the environment. This study evaluated the impact of a large WWTP serving 125,000 people on the Iskar River in Bulgaria, by characterizing the spatial and short-term temporal dynamics in bacterial community dynamics and resistance profiles of the surface water. Pairs of samples were collected biweekly on four dates from two different locations, one about 800 m after the WWTP effluents and the other 10 km downstream. Taxonomic classification revealed the dominance of and , notably the genera , , , , and . The taxonomic structure corresponded with both lentic and lotic freshwater habitats, with exhibiting a significant decrease over the study period. Principal Coordinate Analysis revealed statistically significant differences in bacterial community composition between samples collected on different dates. Differential abundance analysis identified notable enrichment of and There were shifts within the enriched or depleted bacterial taxa between early and late sampling dates. High relative abundance of the genes , , , (macrolides); , , , and (tetracyclines); and (sulphonamides); and , (beta-lactams) were detected, with trends of increased presence in the latest sampling dates and in the location closer to the WWTP. Of note, genes conferring resistance to carbapenems OXA-58 and IMP-33-like were identified. Co-occurrence analysis of ARGs and mobile genetic elements on putative plasmids showed few instances, and the estimated human health risk score (0.19) according to MetaCompare2.0 was low. In total, 29 metagenome-assembled genomes were recovered, with only a few harbouring ARGs. This study enhances our understanding of freshwater microbial community dynamics and antibiotic resistance profiles, highlighting the need for continued ARGs monitoring.
PubMed: 38930632
DOI: 10.3390/microorganisms12061250 -
Microorganisms Jun 2024Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical...
Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical application of antibiotics could potentially facilitate the selection of antibiotic resistance in bacteria, yet no studies have investigated antibiotic use in the retail ornamental fish sector and its impact on microbial communities. The present study analyzed the concentrations of twenty antibiotics in the carriage water (which also originates from fish tanks in retail shops) collected monthly from ten local ornamental fish shops over a duration of three months. The antibiotic concentrations were correlated with the sequenced microbial community composition, and the risk of resistance selection in bacteria was assessed. Results revealed that the detected concentrations of tetracyclines were the highest among samples, followed by fluoroquinolones and macrolides. The concentrations of oxytetracycline (44.3 to 2,262,064.2 ng L) detected across three months demonstrated a high risk for resistance selection at most of the sampled shops. Zoonotic pathogens (species of , , and ) were positively correlated with the concentrations of oxytetracycline, tetracycline, chlortetracycline, and enrofloxacin. This suggests that antibiotic use in retail shops may increase the likelihood of selecting for zoonotic pathogens. These findings shed light on the potential for ornamental fish retail shops to create a favorable environment for the selection of pathogens with antibiotics, thereby highlighting the urgent need for enhanced antibiotic stewardship within the industry.
PubMed: 38930567
DOI: 10.3390/microorganisms12061184 -
Microorganisms May 2024Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic,... (Review)
Review
Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion.
Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID.
PubMed: 38930460
DOI: 10.3390/microorganisms12061078 -
Life (Basel, Switzerland) May 2024pneumonia (MPP) is a frequent cause of community-acquired pneumonia (CAP) in children. The incidence of childhood pneumonia caused by infection has been rapidly...
pneumonia (MPP) is a frequent cause of community-acquired pneumonia (CAP) in children. The incidence of childhood pneumonia caused by infection has been rapidly increasing worldwide. is naturally resistant to beta-lactam antibiotics due to its lack of a cell wall. Macrolides and related antibiotics are considered the optimal drugs for treating infection. However, clinical resistance to macrolides has become a global concern in recent years. Therefore, it is imperative to urgently identify new targets and develop new anti- drugs to treat MMP. Previous studies have shown that deficiencies in HPrK/P kinase or phosphorylase activity can seriously affect carbon metabolism, growth, morphology, and other cellular functions of . To identify potential drug development targets against , this study analyzed the sequence homology and 3D structure alignment of HPrK/P. Through sequence and structure analysis, we found that HPrK/P lacks homologous proteins in the human, while its functional motifs are highly conserved in bacteria. This renders it a promising candidate for drug development. Structure-based virtual screening was then used to discover potential inhibitors among 2614 FDA-approved drugs and 948 bioactive small molecules for HPrK/P. Finally, we identified three candidate drugs (Folic acid, Protokylol and Gluconolactone) as potential HPrK/P inhibitors through molecular docking, molecular dynamics (MDs) simulations, and ADMET predictions. These drugs offer new strategies for the treatment of MPP.
PubMed: 38929642
DOI: 10.3390/life14060657