Plasma miR-19b, miR-34a and miR-146a expression in patients with type 2 diabetes mellitus and cataract: A pilot study.

Cataract is among the most common ocular complications in diabetes mellitus (DM). While microRNA (miRNA) dysregulations in DM have been previously reported, consensus is still lacking concerning miRNA expression in cataract. Furthermore, the miRNA profile in diabetic cataract patients remains largely unexplored, and data on plasma expression levels are limited. Our study aimed to assess the plasma levels of three distinct miRNA species (hsa-miR-19b, hsa-miR-34a, and hsa-miR-146a) implicated in the development of cataract and/or DM. We investigated the circulating miRNA expression in DM patients diagnosed with cataract, compared to a non-DM cataract group. We employed qRT-PCR for relative quantification experiments and subsequently conducted a correlation analysis between miRNA expression levels and clinical characteristics. Our findings reveal that hsa-miR-34a and hsa-miR-146a are differentially expressed in the two cohorts. However, no significant correlation was observed between the clinical variables and miRNA levels. In summary, our results suggest a potential role for hsa-miR-34a and hsa-miR-146a in the biology of diabetic cataract.

Plasma miR-195-5p predicts the severity of Covid-19 in hospitalized patients.

Predicting the clinical course of Covid-19 is a challenging task, given the multi-systemic character of the disease and the paucity of minimally invasive biomarkers of disease severity. Here, we evaluated the early (first two days post-admission) level of circulating hsa-miR-195-5p (miR-195, a known responder to viral infections and SARS-CoV-2 interactor) in Covid-19 patients and assessed its potential as a biomarker of disease severity. We show that plasma miR-195 correlates with several clinical and paraclinical parameters, and is an excellent discriminator between the severe and mild forms of the disease. Our Gene Ontology analysis of miR-195 targets differentially expressed in Covid-19 indicates a strong impact on cardiac mitochondria homeostasis, suggesting a possible role in long Covid and chronic fatigue syndrome (CFS) syndromes.

Current State of Knowledge Regarding WHO High Priority Pathogens-Resistance Mechanisms and Proposed Solutions through Candidates Such as Essential Oils: A Systematic Review.

Combating antimicrobial resistance (AMR) is among the 10 global health issues identified by the World Health Organization (WHO) in 2021. While AMR is a naturally occurring process, the inappropriate use of antibiotics in different settings and legislative gaps has led to its rapid progression. As a result, AMR has grown into a serious global menace that impacts not only humans but also animals and, ultimately, the entire environment. Thus, effective prophylactic measures, as well as more potent and non-toxic antimicrobial agents, are pressingly needed. The antimicrobial activity of essential oils (EOs) is supported by consistent research in the field. Although EOs have been used for centuries, they are newcomers when it comes to managing infections in clinical settings; it is mainly because methodological settings are largely non-overlapping and there are insufficient data regarding EOs' in vivo activity and toxicity. This review considers the concept of AMR and its main determinants, the modality by which the issue has been globally addressed and the potential of EOs as alternative or auxiliary therapy. The focus is shifted towards the pathogenesis, mechanism of resistance and activity of several EOs against the six high priority pathogens listed by WHO in 2017, for which new therapeutic solutions are pressingly required.

Sex-Related Differences in the Pharmacological Response in SARS-CoV-2 Infection, Dyslipidemia, and Diabetes Mellitus: A Narrative Review.

Pharmacological responses vary by sex in several illnesses. This narrative review summarizes sex variations in pharmaceutical response in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Infection with SARS-CoV-2 is more severe and deadly in men than women. This may be attributed to immunological responses, genetics, and hormones. Some research shows that men may respond better to genomic vaccinations and females to antiviral medications such as remdesivir (Moderna and Pfizer-BioNTech). In dyslipidemia, women tend to have greater HDL-C and lower LDL-C than men. Some studies show that females may need lower statin dosages than men to obtain equal LDL-C reductions. Ezetimibe co-administered with a statin significantly improved lipid profile indicators in men compared to women. Statins reduce dementia risk. Atorvastatin decreased dementia risk in males (adjusted HR 0.92, 95% CI 0.88-0.97), whereas lovastatin lowered dementia risk in women (HR 0.74, 95% CI 0.58-0.95). In diabetes mellitus, evidence suggests that females may have a higher risk of developing certain complications such as diabetic retinopathy and neuropathy, despite having lower rates of cardiovascular disease than males. This could be the result of differences in hormonal influences and genetic factors. Some research shows females may respond better to oral hypoglycemic medications such as metformin. In conclusion, sex-related differences in pharmacological response have been observed in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Further research is needed to better understand these differences and to develop personalized treatment strategies for males and females with these conditions.

Identification of Genomic Variants of SARS-CoV-2 Using Nanopore Sequencing.

Background and Objectives: SARS-CoV-2 is the first global threat and life-changing event of the twenty-first century. Although efficient treatments and vaccines have been developed, due to the virus's ability to mutate in key regions of the genome, whole viral genome sequencing is needed for efficient monitoring, evaluation of the spread, and even the adjustment of the molecular diagnostic assays. Materials and Methods: In this study, Nanopore and Ion Torrent sequencing technologies were used to detect the main SARS-CoV-2 circulating strains in Timis County, Romania, between February 2021 and May 2022. Results: We identified 22 virus lineages belonging to seven clades: 20A, 20I (Alpha, V1), 21B (Kappa), 21I (Delta), 21J (Delta), 21K (Omicron), and 21L (Omicron). Conclusions: Results obtained with both methods are comparable, and we confirm the utility of Nanopore sequencing in large-scale epidemiological surveillance due to the lower cost and reduced time for library preparation.

Current State of Knowledge Regarding WHO Critical Priority Pathogens: Mechanisms of Resistance and Proposed Solutions through Candidates Such as Essential Oils.

The rise of multidrug-resistant (MDR) pathogens has become a global health threat and an economic burden in providing adequate and effective treatment for many infections. This large-scale concern has emerged mainly due to mishandling of antibiotics (ABs) and has resulted in the rapid expansion of antimicrobial resistance (AMR). Nowadays, there is an urgent need for more potent, non-toxic and effective antimicrobial agents against MDR strains. In this regard, clinicians, pharmacists, microbiologists and the entire scientific community are encouraged to find alternative solutions in treating infectious diseases cause by these strains. In its "10 global issues to track in 2021", the World Health Organization (WHO) has made fighting drug resistance a priority. It has also issued a list of bacteria that are in urgent need for new ABs. Despite all available resources, researchers are unable to keep the pace of finding novel ABs in the face of emerging MDR strains. Traditional methods are increasingly becoming ineffective, so new approaches need to be considered. In this regard, the general tendency of turning towards natural alternatives has reinforced the interest in essential oils (EOs) as potent antimicrobial agents. Our present article aims to first review the main pathogens classified by WHO as critical in terms of current AMR. The next objective is to summarize the most important and up-to-date aspects of resistance mechanisms to classical antibiotic therapy and to compare them with the latest findings regarding the efficacy of alternative essential oil therapy.

Sex-Related Differences in Pharmacological Response to CNS Drugs: A Narrative Review.

In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men and women significantly influence the pharmacokinetics and pharmacodynamics of drugs. Sex-related differences in central nervous system (CNS) medication are particularly challenging to assess due to the complexity of disease manifestation, drugs' intricate mechanisms of action, and lack of trustworthy means of evaluating the clinical response to medication. Although many studies showed contrary results, it appears to be a general tendency towards a certain sex-related difference in each pharmacological class. Broadly, opioids seem to produce better analgesia in women especially when they are administered for a prolonged period of time. On the other hand, respiratory and gastrointestinal adverse drug reactions (ADRs) following morphine therapy are more prevalent among female patients. Regarding antidepressants, studies suggest that males might respond better to tricyclic antidepressants (TCAs), whereas females prefer selective serotonin reuptake inhibitors (SSRI), probably due to their tolerance to particular ADRs. In general, studies missed spotting any significant sex-related differences in the therapeutic effect of antiepileptic drugs (AED), but ADRs have sex variations in conjunction with sex hormones' metabolism. On the subject of antipsychotic therapy, women appear to have a superior response to this pharmacological class, although there are also studies claiming the opposite. However, it seems that reported sex-related differences regarding ADRs are steadier: women are more at risk of developing various side effects, such as metabolic dysfunctions, cardiovascular disorders, and hyperprolactinemia. Taking all of the above into account, it seems that response to CNS drugs might be occasionally influenced by sex as a biological variable. Nonetheless, although for each pharmacological class, studies generally converge to a certain pattern, opposite outcomes are standing in the way of a clear consensus. Hence, the fact that so many studies are yielding conflicting results emphasizes once again the need to address sex-related differences in pharmacological response to drugs.

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems-Instrumental Screening.

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.