Ali Mazloum

The insulin gene (INS) encodes a peptide hormone critical for glucose homeostasis, and its dysregulation underlies both type 1 and type 2 diabetes mellitus. This review compares the structural organization and functional regulation of the insulin gene in humans and mice, highlighting key species differences including the presence of two non-allelic insulin genes (Ins1 and Ins2) in mice versus a single INS gene in humans. Despite these differences, most preclinical diabetes research has historically been conducted in male mice, potentially concealing sex and species specific mechanisms. Additionally, this review examines the growing evidence for sex-specific differences in diabetes susceptibility. Recent single-cell multi-omics studies reveal that human pancreatic islets exhibit sex-specific chromatin accessibility and gene expression patterns, with autosomal sex differences emerging predominantly in type 2 diabetes. The protective effects of estrogen, mediated through estrogen receptor α signaling, contribute to enhanced insulin sensitivity and beta-cell function in premenopausal females. We argue that routine inclusion of both sexes and species aware interpretation of insulin gene studies are prerequisites for precision diabetology.

Animal infectious diseases impose severe economic burdens on livestock industries, threaten wildlife populations, and compromise food security. Although vaccination remains the cornerstone of disease prevention, conventional vaccine platforms are often constrained by safety, efficacy, or manufacturing scalability. This narrative review provides a comprehensive analysis of the state of the art in herpesvirus-vectored vaccines for veterinary applications, focusing on five well-characterized alphaherpesviruses: Bovine herpesvirus type 1 (BoHV-1), Pseudorabies virus (PRV), Marek’s disease virus (MDV), Equine herpesvirus type 1 (EHV-1), and Duck enteritis virus (DEV). The intrinsic characteristics of herpesviruses, including large, stable genomes; the capacity for foreign gene insertion; broad host tropism; and the ability to elicit robust humoral and cellular immunity, are examined, and their performance is compared with that of traditional vaccine platforms. Key advances in vectored vaccine development are highlighted, from proof-of-concept studies to the creation of advanced multivalent constructs. These approaches demonstrate protective efficacy against a range of significant animal pathogens, including foot-and-mouth disease virus, porcine reproductive and respiratory syndrome virus, avian influenza virus, infectious bursal disease virus, and West Nile virus. The literature was identified through systematic searches of PubMed, Google Scholar, and Web of Science (1990–2026), followed by title/abstract screening and reference chaining. Future directions in vector engineering, mucosal delivery, and synthetic biology approaches are considered. Herpesvirus-vectored vaccines represent a versatile platform for enhancing animal health, supporting sustainable agriculture, and mitigating zoonotic risks.

The liver is a primary metabolic hub and a pivotal target for gene therapy, owing to its capacity for protein secretion, role in metabolic homeostasis and immune tolerance. Liver-directed gene therapies are used to treat numerous inherited metabolic disorders and coagulation factor deficiencies including hemophilia (A and B), Crigler–Najjar syndrome, mucopolysaccharidoses, phenylketonuria, Fabry, Gaucher, Wilson and Pompe diseases. The efficacy and safety of liver-directed gene therapy rely on the use of strong tissue-specific promoters. To date, there are many different liver-specific promoters used in preclinical and clinical studies, including novel completely synthetic promoters. This review provides a comprehensive analysis of the design, engineering and application of liver-specific promoters. Furthermore, we discuss fundamental principles of gene expression regulation in the liver and the physiological and immunological characteristics that make it a suitable target organ for gene therapy delivery.

X-linked adrenoleukodystrophy (X-ALD) is a monogenic progressive neurodegenerative disorder, being simultaneously a systemic metabolic disease and demonstrating severe neurological manifestations with effects to the brain and spinal cord. The objective of the current review is to provide a detailed approach to adeno-associated virus (AAV)-based gene therapy for neurological manifestations of X-ALD. The development of a successful AAV-mediated gene therapy hinges on its ability to deliver ABCD1 cDNA effectively to the relevant organs and cell types, induce therapeutic levels of protein expression, and ultimately, restore normal very-long chain fatty acids (VLCFA) metabolic function. Thus, several key considerations should be addressed when designing AAV-based gene therapy for X-ALD, including the genetic background of the disease and requisite transgene expression levels, the biochemical function of the adrenoleukodystrophy protein (ALDP), the identification of target cells and their role in pathogenesis, the regulation of expression within the genetic construct, the route of administration, the selection of an AAV serotype with high tropism for the central and peripheral nervous systems, and the development of robust in vitro and in vivo models.

Maturity-onset diabetes of the young type 10 (MODY10) is a monogenic diabetes subtype caused by heterozygous mutations in the insulin gene (INS), leading to defective proinsulin processing, endoplasmic reticulum (ER) stress, and β-cell dysfunction. Current management relies on sulfonylureas or insulin therapy, but these fail to address the underlying genetic defect. Recent research has elucidated the molecular mechanisms of MODY10, including ER stress induced by proinsulin misfolding, activation of the unfolded protein response (UPR), and β-cell apoptosis. Emerging therapies such as Adeno-Associated Virus (AAV)-mediated gene delivery to induce the glucose-responsive hepatic insulin expression, plasmid-based single-chain insulin analogs, and cell-based therapies show promise in preclinical studies. However, critical challenges remain, including immune responses to AAV vectors, incomplete correction of dominant-negative mutant effects, and the need for long-term safety data. This review summarizes current knowledge on MODY10 genetics, pathophysiology, and therapeutic innovations, while identifying key gaps for future research to enable precision medicine approaches.

The lack of data on the whole-genome analysis of genotype II African swine fever virus (ASFV) isolates significantly hinders our understanding of its molecular evolution, and as a result, the range of single nucleotide polymorphisms (SNPs) necessary to describe a more accurate and complete scheme of its circulation. In this regard, this study aimed to identify unique SNPs, conduct phylogenetic analysis, and determine the level of homology of isolates obtained in the period from 2019 to 2022 in the central and eastern regions of Russia. Twenty-one whole-genome sequences of genotype II ASFV isolates were assembled, analyzed, and submitted to GenBank. The isolates in eastern Russia form two clades, “Amur 2022” and “Asia”. Within the latter clade, five subclusters can be distinguished, each characterized by a unique set of SNPs and indels. The isolates from the central regions of Russia (2019; 2021) form the “Center of Russia” clade, with two subclusters, “Bryansk 2021” and “Center of Russia 2021” (bootstrap confidence index = 99). The presence of the previously unique genetic variant ASFV for the Kaliningrad region in the wild boar population of the Khabarovsk region (eastern Russia; 2021) has also been confirmed.

Introduction African swine fever (ASF) is a contagious viral disease that affects pigs and wild boars, with a mortality rate of up to 100% in susceptible animals. The virus has been circulating in Europe and Asia since its introduction in 2007. Initially, all studied isolates were identified as genotype II, but in 2021 genotype I was reported in China. Later in 2023, the first recombinant virus of genotype I and II was identified in China, with an isolate dating back to 2021, this was followed by the detection of 6 recombinant isolates in Vietnam. Methods In this study, an ASFV isolate from the Primorsky Region of Russia obtained from a domestic pig was analyzed by sequencing several genome markers as well as the full genome. Eight pigs were infected with the isolate to assess its virulence. Results Virus replication in cell culture showed hemadsorption, while sequencing of genome markers clustered the isolate into both genotype I and genotype II. The whole-genome sequence showed that the Russian isolate shared a 99.99% identity with recombinant isolates described earlier in China. Experimental animals developed ASF disease after the introduction of a low dose of the virus (10 HAU50) and died within 7 days post-infection, presenting an acute form of the disease. Conclusion This is the first report on recombinant ASFV in Russia’s territory. The results once again confirm the transboundary nature of the disease, demonstrating the vulnerability of the global pig industry underscoring the need for developing new ASF vaccines effective against recombinant strains and emphasizing the importance of continuous molecular monitoring to detect emerging threats promptly.

Classical swine fever (CSF) remains a challenge for pig farming industrial lover the world despite the measures taken. The last CS case in the Russian Federation was reported in 2020, however, the threat of the disease emerging still persists. A set of anti-epidemic measures including mainly preventive vaccination and annual diagnostic monitoring using molecular-genetic and serological methods is required for CSF virus introduction prevention and rapid eradication of potential disease out breaks. Therefore, areal-time reverse transcription-polymerase chain reaction using an internal control sample has been developed. Therefore, areal time reverse transcription-polymerase chain reaction using an internal control sample has been developed. Modified primers (locked nucleic acids containing conformationally blocked nucleosides) providing a higher affinity to the DNA matrix and physico-chemical stability and a FAM-labeled TaqMan probe were selected for 5’-untranslatedregion of the genome. The following validation parameters were defined: accuracy, repeatability, reproducibility, specificity and sensitivity. For comparative analysis of the developed as say sensitivity, swabs, samples of organs and tissues collected from pigs experimentally infected with an epizootic strain of the classical swine fever virus (spleen, kidney, liver, blood, lymph nodes, rectal and oral smears), animal-contaminated feed and virus-containing material with known virus titres were also tested in parallel with coded test systems No. x1 andx2. The developed assay was shown to have 100% diagnostic sensitivity and detection limit of 0,23 lgCCID₅₀/cm³. Therewith, there sults of analysis of test systems No. x1, x2 based on above parameters were lower that could give rise to false positive real-time RT-PCR results and incorrect diagnosis. Thus, described assay can be used for extensive monitoring of classical swine fever in the Russian Federation

As part of extensive molecular and genetic research into African swine fever virus isolates circulating in Russia, a recombinant variant with a mosaic genome structure has been identified. The one that caused an outbreak on a pig farm in the Primorsky Krai, in 2023. The characterized strain ASFV/Primorsky_2023/DP-4560.Recdemonstrates hemadsorption, active propagation in porcine primary macrophage cell culture, 99.9917% identity with the first recombinant isolates from the People’s Republic of China, recovered in 2021. Recombination sites included 79 open reading frames homologous to genotype II isolates; 49 ones homologous to genotype I and 12 mixed ones. Testing biomaterial from dead pigs in real-time polymerase chain reaction showed no changes in sensitivity or specificity, despite significant genetic distinctions between the recombinant and genotype II isolates that are enzootic to the Russian Federation. However, in 2023, D. Zhao et al. reported on high virulence of the virus related variants as revealed by the challenge tests in domestic pigs. Given the accelerating rates of AFSV molecular evolution in the East Asian countries (China, Vietnam and the Far Eastern regions of Russia), it is required to improve control measures, general and specific prevention, national and international surveillance over the economically significant animal disease.

Introduction. The rapid spread of African swine fever in the Kaliningrad region makes it necessary to use the methods of molecular epidemiology to determine the dynamics and direction of ASF spread in this region of Russia. The aim of the study was to determine single nucleotide polymorphisms within molecular markers K145R, O174L and MGF 505-5R of ASFVs isolated in Kaliningrad region and to study the circulating of the pathogen in European countries by subgenotyping and spatio-temporal clustering analysis. Materials and methods. Blood samples from living domestic pigs and organs from dead domestic pigs and wild boars, collected in the Kaliningrad region between 2017 and 2022 were used. Virus isolation was carried out in porcine bone-marrow primary cell culture. Amplicons of genome markers were amplified by PCR with electrophoretic detection and subsequent extraction of fragments from agarose gel. Sequencing was performed using the Sanger method. Results. The circulation of two genetic clusters of ASFV isolates on the territory of the Kaliningrad has been established: epidemic (K145R-III, MGF 505-5R-II, O174L-I – 94.3% of the studied isolates) and sporadic (K145R-II, MGF 505-5R-II, O174L-I – 5.7%). Conclusion. The broaden molecular genetic surveillance of ASFV isolates based on sequencing of genome markers is necessary in the countries of the Eurasian continent to perform a more detailed analysis of ASF spread between countries and within regions.