N-protein vaccine is effective against COVID-19: Phase 3, randomized, double-blind, placebo-controlled clinical trial.

Background: Despite the success of first-generation COVID-19 vaccines targeting the spike (S) protein, emerging SARS-CoV-2 variants have led to immune escape, reducing the efficacy of these vaccines. Additionally, some individuals are unable to mount an effective immune response to S protein-based vaccines. This has created a need for alternative vaccine strategies that are less susceptible to mutations and capable of providing broad and durable protection.

Analysis of Clinical Success and Molecular Mechanisms of Action of Novel Anti-glioblastoma Drugs: A Review.

Background: Gliomas and glioblastomas (GBM) are common primary malignant brain tumors, which are highly malignant and have a poor prognosis. The presence of cancer stem cells with unrestricted proliferative capacity and ability to generate glial neoplastic cells, the diffuse nature of GBM, and other specific factors of GBM contribute to poor results of drug therapy in patients with GBM. Despite the worldwide efforts to improve the treatment, many novel anti-GBM drugs are active just in vitro, in silico, and in preclinical trials, and they sometimes demonstrate poor or no activity in clinical trials.

[Experience with the use of pharmacopoeial reference material for the activity of measles vaccine].

Introduction: Due to the increased incidence of measles in Russia and in many other regions of the world, vaccines for the measles prevention are especially in demand. Ensuring the quality of the measles vaccine for effective disease prevention is within the scope of the tasks of the state policy of our country.

Objective: Evaluation of the experience of using a pharmacopoeial standard material of measles vaccine activity for measurement of the specific activity of the measles virus in vaccines with a measles component that are used in the Russian Federation for measles prevention.

Simultaneous Determination of General Active Ingredients in Topical Formulations by Gas Chromatography with Flame Ionization Detection (GC-FID).

A simple, fast, precision and sensitive gas chromatographic method was developed for determination of camphor, L-menthol, methyl salicylate, salicylic acid, benzyl nicotinate and nonivamide in topical formulations. The possibility of determination low-boiling components and high-boiling components by a single analytical method was shown. The method was optimized by evaluating the effect of a large number of chromatographic parameters and sample preparation stages.

The Influence of Atorvastatin, Amlodipine and Ethoxidol on Ubiquinol and Ubiquinone Endogenous Plasma Concentrations in Patients with Chronic Heart Failure.

Background: Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain almost uninvestigated.

[Pharmacoeconomic evaluation of the tixagevimab and cilgavimab combination using for pre-exposure prophylaxis of COVID-19].

Aim: To evaluate pharmacoeconomic feasibility using of the tixagevimab and cilgavimab combination for pre-exposure prophylaxis of COVID-19 in immunocompromised patients.

Materials And Methods: Cost-effectiveness of tixagevimab and cilgavimab in persons ≥12 years old who weigh ≥40 kg and have either a history of allergy that prevents their vaccination against COVID-19 or moderate or immunocompromised was assessed based on PROVENT phase III study results. The quantity of life years or quality-adjusted life years gained was calculated.

Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation.

Background: Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation MIR 19® (siR-7-EM/KK-46) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19.

Methods: We conducted an open-label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR-7-EM/KK-46 (3.

The Influence of Structural Variants of the Gene on the Pharmacokinetics of Enalapril, Presumably Due to Linkage Disequilibrium with the Intronic rs2244613.

Variants in the gene encoding carboxylesterase 1 may affect the metabolism of enalapril to the active metabolite enalaprilat. It was shown that the A allele of rs71647871 and the C allele of rs2244613 led to a decrease in plasma enalaprilat concentrations. This study aimed to estimate the effect of structural haplotypes of containing the pseudogene or a hybrid of the gene and the pseudogene on the pharmacokinetics of enalapril.

Combination of immune checkpoint inhibitors with radiation therapy in cancer: A hammer breaking the wall of resistance.

Immuno-oncology is an emerging field in the treatment of oncological diseases, that is based on recruitment of the host immune system to attack the tumor. Radiation exposure may help to unlock the potential of the immune activating agents by enhancing the antigen release and presentation, attraction of immunocompetent cells to the inflammation site, and eliminating the tumor cells by phagocytosis, thereby leading to an overall enhancement of the immune response. Numerous preclinical studies in mouse models of glioma, murine melanoma, extracranial cancer, or colorectal cancer have contributed to determination of the optimal radiotherapy fractionation, as well as the radio- and immunotherapy sequencing strategies for maximizing the antitumor activity of the treatment regimen.

Novel Hydroxypyridine Compound Protects Brain Cells against Ischemic Damage In Vitro and In Vivo.

A non-surgical pharmacological approach to control cellular vitality and functionality during ischemic and/or reperfusion-induced phases of strokes remains extremely important. The synthesis of 2-ethyl-6-methyl-3-hydroxypyridinium gammalactone-2,3-dehydro-L-gulonate (3-EA) was performed using a topochemical reaction. The cell-protective effects of 3-EA were studied on a model of glutamate excitotoxicity (GluTox) and glucose-oxygen deprivation (OGD) in a culture of NMRI mice cortical cells.

[Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19].

The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg.

Potential factors of resistance to clarithromycin.

Objectives: A comparative dissolution kinetics test (CDKT) and bioequivalence studies of generic proton pump inhibitors (PPIs) do not model pharmacological acid suppression (PAS) and pathological duodenogastric reflux (PDGR). This study aimed to model them in CDKT to assess drugs stability and potential pantoprazole-clarithromycin interactions.

Methods: In CDKT, PDGR (dissolution medium pH 7.

Development of a Quantitative Determination Method for Aluminum Ions in Adsorbed Drugs Using Atomic Absorption Spectrometry with Electrothermal Atomization.

A quantitative determination method for Al in immunobiological drugs using atomic absorption spectroscopy with electrothermal atomization was developed. Conditions for the preparation of aluminum hydroxide gel were selected [NaOH (5 M), heating in a boiling-water bath for 5 min followed by neutralization with conc. HNO].

Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps. A workshop Report.

This online workshop Accelerating Global Deletion of the Abnormal Toxicity Test for vaccines and biologicals. Planning common next steps was organized on October 14th, 2021, by the Animal Free Safety Assessment Collaboration (AFSA), the Humane Society International (HSI), the European Federation of Pharmaceutical Industries and Associations (EFPIA), in collaboration with the International Alliance of Biological Standardization (IABS). The workshop saw a participation of over a hundred representatives from international organizations, pharmaceutical industries and associations, and regulatory authorities of 28 countries.

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems.

The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods.

Quantitative Assay of B. pertussis Lipopolysaccharide.

We studied activity of Bordetella pertussis LPS in the LAL test. The mean activity of various series of LPS preparations obtained from B. pertussis cells ranged from 1,950,000 to 2,940,000 endotoxin units/μg (EU/μg).

WHO informal consultation on revision of guidelines on evaluation of similar biotherapeutic products, virtual meeting, 30 June - 2 July 2021.

The WHO informal consultation was held to promote the revision of WHO guidelines on evaluation of similar biotherapeutic products (SBPs) adopted by the Expert Committee on Biological Standardization (ECBS) in 2009. It was agreed in the past consultations that the evaluation principles in the guidelines are still valid, but a review was recommended to provide more clarity and case-by-case flexibility. The opportunity was therefore taken to review the experience and identify areas where the current guidance could be more permissive without compromising its basic principles, and where additional explanation could be provided regarding the possibility of reducing the amount of data needed for regulatory approval.

The Influence of the Genotype on the Pharmacokinetics of Enalapril in Patients with Arterial Hypertension.

The angiotensin-converting enzyme inhibitor enalapril is hydrolysed to an active metabolite, enalaprilat, in the liver via carboxylesterase 1 (CES1). Previous studies show that variant rs71647871 in the CES1 gene affects the pharmacokinetics of enalapril on liver samples as well as healthy volunteers. This study included 286 Caucasian patients with arterial hypertension who received enalapril.

Gastroprotective effect of on ethanol-induced gastric mucosal injury: Histopathological evaluations.

Objective: Modern treatment of peptic ulcers includes antibacterial and gastroprotective medications. However, current anti-ulcer drugs possess severe side effects. Therefore, all attempts to find new effective medications free from side effects are justified.

[Myostatin - a modern understanding of the physiological role and significance in the development of age-associated diseases.].

Myostatin is a protein belonging to the myokine class, the family of transforming growth factors β (TGF-β). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions.

Development and Validation of four Nitrosamine Impurities Determination Method in Medicines of Valsartan, Losartan, and Irbesartan with HPLC-MS/MS (APCI).

Since 2018, regulation and control of genotoxic nitrosamine impurities levels have been a mandatory quality and safety characteristic for various drugs. The main issue of nitrosamine determination in drugs is a low sensitivity of the existing methods and a continuously extending list of controlled compounds. The reason is the low safe daily dose of these impurities and chromophores' absence within their structure.

Follistatin-Like Proteins: Structure, Functions and Biomedical Importance.

Main forms of cellular signal transmission are known to be autocrine and paracrine signaling. Several cells secrete messengers called autocrine or paracrine agents that can bind the corresponding receptors on the surface of the cells themselves or their microenvironment. Follistatin and follistatin-like proteins can be called one of the most important bifunctional messengers capable of displaying both autocrine and paracrine activity.

The distributed ledger technology as a measure to minimize risks of poor-quality pharmaceuticals circulation.

Background: In the modern world, millions of people suffer from fake and poor-quality medical products entering the market. Violation of the rules of transportation of drugs makes them ineffective and even dangerous. The relationship between the various parts of the supply chain, production and regulation of drugs is too hard and has many problems.

Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy.

The authors developed a H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher's test, and Student's -test for assay results.