Molecular Biology Reports最新文献

Background: Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 inhibitor and is used in the treatment of diabetes. In this study, we aimed to investigate the effect of DPG on cardiotoxicity caused by systemic inflammation via endoplasmic reticulum (ER) stress and autophagy.

Methods and results: Four groups of thirty-two Wistar Albino rats were created: Control (1 ml oral physiological saline for five days and intraperitoneal saline on the 5th day), LPS (1 ml oral physiological saline for five days and intraperitoneal 5 mg/kg of LPS on the 5th day), LPS + DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of LPS intraperitoneally on the 5th day), and DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of SF intraperitoneally on the 5th day). Histopathological and immunohistochemical analyses were performed on heart and aorta tissues. ER stress and autophagy gene markers in heart tissues were evaluated by RT-qPCR. Oxidative stress in heart tissues and serum cardiac enzymes were analyzed by spectrophotometric method. The heart and aortic tissues of the LPS group showed increased expressions of Tumor Necrosis Factor-α (TNF-α) and Caspase-3 (Cas-3), along with mild hyperemia, slight inflammatory cell infiltrations, and myocardial cell damage. The heart tissues also showed genetically increased expressions of include binding immunoglobulin protein (BiP/ GRP78), protein kinase RNA-like ER Kinase (PERK), inositol-requiring enzyme 1 (IRE-1), activating transcription factors 4 (ATF-4), activating transcription factors 4 (ATF6), C/EBP homologous protein (CHOP), and BECLIN 1. Furthermore, Creatine kinase-MB (CK-MB) and Lactate dehydrogenase (LDH) levels in blood tissue significantly increased, according to biochemical analysis. With DPG therapy, all of these findings were reversed.

Conclusion: In conclusion, DPG protects against the cardiotoxic effect of systemic inflammation with its antioxidant and anti-inflammatory properties by regulating ER stress and autophagy pathways.

Patients with severe COVID-19 may be more likely to develop PD as a result of shared biological pathways including a great expansion of MDSCs and an imbalance in Th17/Tregs ratio. We think that these shared pathogenic features may mechanistically explain the COVID-19 - PD axis. Thus, we assume that patients who recovered from critical COVID-19 should be selected based upon a potential higher risk of developing PD. Further studies are needed to better define the possible relationship between COVID-19 and neuroinflammation and identify whether some people are more likely to develop PD after contracting COVID-19 than others with special emphasis to ascertain possible vulnerable genetic backgrounds or epigenetic factors acting on brain which may promote PD during SARS COV-2 infection. Finally, we think that regular physical activity should be performed and encouraged in patients with PD.

Background: Doublesex and mab-3 related transcription factor (DMRT) 1, commonly found in all vertebrates, regulates the transcription of genes involved in the masculinization and maintenance of gonadal somatic cells and/or germline cell development. DMRT1 has a DNA-binding domain called the DM domain and a transcription regulatory region. Unlike the former, there is little knowledge about the latter transcription regulatory region. This study aimed to identify the transcription activation regions of DMRT1 from four species: humans and mice (mammals), leopard geckos (reptiles), and medaka (teleost fish), adding perspectives on evolutionary conservation and diversity.

Methods and results: For each species, several expression plasmids of deletion mutants were constructed, and the resultant plasmid and a DMRT1-driven luciferase reporter were co-transfected into cultured cells to measure transactivation ability. The key point of this analysis is that the transactivation ability was normalized by quantifying the expression levels of DMRT1 variants using the HiBiT tag. As a result, two to three transactivation regions were suggested to exist in the C-terminal region of the DM domain in all four species. Among seven regions in DMRT1, the fourth region from the N-terminus contributed to transactivation common to the four species, and the sixth and seventh regions on the C-terminal side differed depending on the species.

Conclusions: These findings indicated that the regions involved in the transactivation ability of DMRT1 could subtly change during evolution, indicating diversity in transactivation domains.

Dyslipidemia is the most significant risk factor for cardiovascular diseases (CVDs) Secondary dyslipidemia: its treatments and association with atherosclerosis. Glob Health Med, Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies. The current treatment strategies for managing dyslipidemia focus on reducing low-density lipoprotein cholesterol (LDL-C) to minimize the risks of atherosclerosis and myocardial infarction (MI). Homozygous Familial Hypercholesterolemia (HoFH) is an inherited autosomal dominant disease caused by a mutation in the LDL receptor (LDLr), which can lead to extremely high levels of LDL-C The Beneficial Effect of Lomitapide on the Cardiovascular System in LDLr(-/-) Mice with Obesity, The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity. Although statin therapy has been the primary treatment for dyslipidemia, HoFH patients do not respond well to statins, requiring alternative therapies. Microsomal triglyceride transfer protein (MTP) inhibition has emerged as a potential therapeutic target for treating HoFH. MTP is primarily responsible for transferring triglyceride and other lipids into apolipoprotein B (ApoB) during the assembly of very low-density lipoprotein (VLDL) particles in the liver. Lomitapide, an inhibitor of MTP, has been approved for treatingof HoFH adults. Unlike statins, lomitapide does not act on the LDLr to reduce cholesterol. Instead, lomitapide lowers the levels of ApoB-containing proteins, primarily VLDL, eventually decreasing LDL-C levels. Studies have shown that lomitapide can reduce LDL-C levels by more than 50% in patients with HoFH who have failed to respond adequately to other treatments. Lowering LDL-C levels is important for preventing atherosclerosis, reducing cardiovascular risk, improving endothelial function, and promoting overall cardiovascular health, especially for patients with HoFH Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. This review paper focuses on research findings regarding the therapeutic benefits of lomitapide, highlighting its effectiveness in lowering cholesterol levels and reducing the risk of CVDs The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity.

Background: We hereby report the first occurrence of Helobdella octatestisaca in North Africa, specifically in Tunisia, as a likely introduced species from the Neotropical Region. Historically, leeches bearing a prominent chitinous scute on their dorsal surface were commonly diagnosed as H. stagnalis. Most probably, H. octatestisaca had previously been misidentified as H. stagnalis in Tunisia.

Methods and results: The identification was primarily based on morphological evidence, supplemented by genetic data obtained from COI DNA barcoding. The morphology of the examined specimens was consistent with the original species description, notably characterized by the presence of four pairs of testisacs. To support our findings, we conducted a phylogenetic analysis using the Maximum Likelihood method based on COI alignment constructed with the newly obtained sequence from Tunisian specimens and complete or nearly complete 'Folmer fragment' sequences of congeners sourced from the GenBank database.

Conclusions: This study highlights the first identification of H. octatestisaca in North Africa and suggests that previous records of H. stagnalis in Tunisia likely misidentified this species.

Background: Given the strong association between high-risk HPV genotypes, such as HPV 16 and 18, and cervical cancer, this study aimed to compare the distribution of common HPV genotypes in the southwest Iranian population with those included in the available vaccines.

Methods: Based on the sample quality, DNA was extracted from the biological samples of 8036 individuals included in the study using three different methods (automated instrument, column, and precipitation), and a total of 21 different HPV genotypes were detected using real-time PCR.

Results: The majority of participants were women (> 99%), with a positive rate of HPV infection of 29.9%, in which high-risk genotypes were dominant in 84.9% cases. The highest rate of HPV infections was observed in the age ≤ 30 years (35.9%). HPV 6 and 16 were the most frequent low- and high-risk genotypes, respectively. Multi HPV infections were observed in 35% of positive samples and the highest cross infections were observed between HPV6 and 16. Co-infection with HPV 16 and 18 was observed in 21 positive samples (1%). Although vaccination is essential to reduce the outcome of HPV infections, such as cervical cancer, other frequently occurring high-risk genotypes are not included in the 9-valent vaccine.

Conclusion: Since the association between cervical cancer and other high-risk HPV types rather than 16 and 18 has been less studied, investigating their pathogenicity in cervical cancer is recommended. Furthermore, the new generation of HPV vaccines should contain other frequently occurring high-risk genotypes beyond those currently covered in approved vaccines.

Background: India's oilseed economy falls short of self-sufficiency and is supplemented by huge imports every year. Increasing national productivity of the major oilseeds is confronted with yield losses due to diverse biotic and abiotic stresses. The productivity of Indian mustard (Brassica juncea Linnaeus), belonging to the family Brassicaceae, is significantly reduced due to damage caused by mustard aphids (Lipaphis erysimi Kaltenbach, Hemiptera: Aphididae). Rapid colonization by the nymphs makes it difficult to protect the crop through agrochemicals. Aphids release effector molecules to modulate the host-defence responses. Glucosinolates (GSLs) extensively found in Brassicaceae family, are hydrolysed by myrosinase into toxic compounds that deter herbivore insects.

Methods: Here, we investigated the differential activation of the glucosinolate-myrosinase pathway in mustard manifesting susceptibility and resistance to different aphid species. Mustard plants were challenged by two different aphid species mustard aphid and cowpea aphid (Aphis craccivora Koch, Hemiptera: Aphididae) leading to complete host-susceptibility in one case and resistance in the other, respectively. Differential regulation of the GSL biosynthetic pathway and myrosinase activity was assessed by gene expression study and ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC- QToF-ESL-MS).

Results: Gene expression study identified selective transcriptional attenuation of the key GSL biosynthetic and myrosinase gene in mustard when challenged with mustard aphid. In contrary, the activation of GSL biosynthetic genes in conjunction with myrosinase at the transcriptional level was profound in mustard, when challenged with cowpea aphid. UPLC-MS analysis showed higher turnover in the hydrolysis of glucosinolates by myrosinase which led to concomitant generation of glucose as byproduct in response to cowpea aphid in mustard plants.

Conclusion: GSL-myrosinase pathway is specifically attenuated by the successful aphid species in mustard and thus plays a pivotal role in determining the outcome of the B. juncea-aphid interaction. The results open up a new genetic modification strategy for developing resistance against aphids.

Background: Drug-resistant tuberculosis not only diminishes treatment efficacy but also heightens the risk of transmission and mortality. Investigating Mycobacterium tuberculosis resistance to first-line antituberculosis drugs is essential to tackle a major global health challenge.

Methods and results: Using Sanger sequencing, this study investigates gene mutations associated with multidrug resistance in drug-resistant M. tuberculosis strains. Among 30 samples, mutations were found in genes linked to first-line anti-tuberculosis drug resistance. Rifampicin resistance was observed in 46.67% of the samples, with the most frequent mutation in the rpoB gene at codon 450 (S450L) occurring in 23.33% of cases. Similarly, isoniazid resistance was found in 86.67% of samples, with 33.33% of cases indicating the katG gene mutation at codon 315 (S315T). Additionally, streptomycin resistance was present in 76.67% of samples, and 30% of these cases were mainly linked to the rpsL gene mutation at codon 43 (K43R).

Conclusion: These findings illuminate the genetic mechanisms behind drug resistance in M. tuberculosis. By identifying specific genetic markers, this research enhances our ability to diagnose and treat drug-resistant Tuberculosis more accurately and efficiently.

Background: Skeletal muscle is a highly adaptive tissue, capable of responding to different physiological and functional demands, even in situations that may cause instability.

Objectives: To evaluate how partial calcaneal tendon (CT) injuries affect the remodeling and plasticity of the gastrocnemius muscle over time.

Methods and results: The study was carried out with Wistar rats randomly divided into five groups. The control group comprised animals not subjected to partial CT damage. The remaining four groups were subjected to partial CT damage and were further categorized based on the time of euthanasia: 3, 14, 28, and 55 days after injury. The gastrocnemius muscle was collected and used for gene expression analysis, zymography, flow cytometry, and morphology. The calcaneal tendon was analyzed only to verify the presence of the partial injury.

Results: The impact of partial CT injury on the gastrocnemius homeostasis, particularly on gene expression, was more pronounced in the 3-day group compared to the other groups, especially the control group. Cytokine profile and morphologic alterations occurred in the 55 days group when compared to the other groups.

Conclusions: The data reported here suggest that partial injury can negatively affect intracellular signaling and degradation pathways, disturbing the muscular extracellular matrix regulatory mechanisms and communication with the tendon. However, skeletal muscle seems to mitigate these harmful effects in comparison with lesions that affect muscle and tendon.