Search Results (63)

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article

Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitative polymerase chain reaction (qPCR) using a ViiA7^® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming to uncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity. Full article

Background/Objectives: This study aimed to examine the effects of a Fucoidan-rich extract from Saccharina latissima (SLE-F) on differential gut microbiota composition, intestinal inflammation status, and microbial functional gene expression in participants infected with Dengue or Oropouche virus at the Hermanos Ameijeiras Hospital in Havana, Cuba. Methods: Fecal samples were collected at baseline, day 28, and day 90 from 90 healthy adults, some of whom contracted the virus during the study period. Functional gene analysis was conducted using two approaches—the Kruskal–Wallis H test and linear discriminant analysis effect size—applied to ortholog-level data normalized by read count and gene copy number. Results: Infected participants exhibited significantly lower Lachnospiraceae-to-Enterobacteriaceae (LE) ratios, indicating increased intestinal inflammation. High-dose SLE-F treatment led to a significant reduction in the LE ratio (p = 0.006), suggesting a strong anti-inflammatory effect. Microbiome analysis revealed a shift from dysbiosis to a more balanced composition by the end of the study, characterized by increased abundances of Akkermansia muciniphila, Bifidobacterium adolescentis, and B. longum, along with decreased pro-inflammatory taxa such as Fusobacterium. Conclusions: Genetic analysis provided distinct yet complementary insights into the microbiome’s functional responses to infection and therapeutic modulation by Fucoidan. These findings highlight the therapeutic potential of high-dose Fucoidan in reducing gut inflammation and promoting microbiome recovery following viral infections. Full article

Background: The success of forensic genetics has led to considerable numbers of DNA samples that must be stored. For example, the genetic casework unit of the forensic institute of the French gendarmerie analyzes more than 70,000 casework samples per year mainly from swabs that are fully consumed during DNA extraction. The only way to process further analyses is to preserve DNA. Currently, the most common technique used for the long-term preservation of DNA is to freeze the extracted DNA at −20 °C or −80 °C. However, this preservation method involves significant constraints (large equipment), risks (equipment failure), and is not ecologically sustainable due to its high energy consumption. Many solutions for DNA preservation at room temperature exist based either on fibrous supports or on anhydrobiosis. However, few studies have examined the efficiency of these systems in preserving very-low DNA amounts, such as those in forensic samples (≤1 ng), while ensuring full recovery and the ability to retest the samples many years later. Methods: We choose to evaluate the ability of the anhydrobiosis technology from GenTegra^® LLC to preserve DNA extracts from one month to one accelerated year from different DNA quantities (from 1 ng to 0.2 ng) and sources (NIST, mocked samples, and true casework mixtures). We studied the quantity, integrity of DNA, and also the quality of the STR genetic profiles obtained. Results and Conclusions: Our results prove the high potential of this technology to preserve and to allow an effective recovery of the DNA extracts for forensic purposes. Full article

Background: Monitoring genetic parameters is important for setting effective conservation and management strategies, particularly for small, fragmented, and isolated populations. Small, isolated populations face increased rates of genetic drift and inbreeding, which increase extinction risk especially when gene flow is limited. Methods: Here, we applied a Genotyping-in-Thousands by sequencing (GT-seq) panel to inform recovery action for the federally threatened northern Idaho ground squirrel (Urocitellus brunneus). We evaluated genetic diversity, structure, connectivity, and effective population size to address species recovery goals. Results: We delineated three types of conservation units: (1) three evolutionarily significant units that represent long-term population structure and variation, (2) nine management units that reflect current demographic connectivity and restrictions to gene flow, and (3) three adaptive units that capture adaptive differentiation across the species range. Effective population sizes per management unit were small overall (mean 38.16, range 2.3–220.9), indicating that recovery goals of 10 subpopulations with N_e > 500 have not been reached. Conclusions: Our results support the maintenance of connectivity within evolutionarily significant units through the restoration of dispersal corridors. Next steps could include further sampling of some subpopulations with low sample sizes, unsampled subpopulations, and subpopulations that are geographically isolated. Genotyping future samples with the same GT-seq panel would help to detect dispersal, assess effective population size, monitor the effects of inbreeding, and evaluate adaptive differentiation to monitor the effects of management action and environmental change. Full article

Background: Oral mucositis (OM) is a painful inflammation resulting from chemotherapy. It is dependent on factors such as age, gender, chemotherapy regimen, oral health, immunological and nutritional status, and genetics. Objectives: The aim of the study was to conduct a narrative review to compile studies on the contribution of genetic and epigenetic aspects to the pathogenesis of OM in children with haematological malignancies undergoing chemotherapy treatment. Methods: The literature search was performed in Pubmed, Scopus, Web of Science, Cochrane, Lilacs, and grey literature databases covering articles published since 2010. Results: Twenty-two studies investigating polymorphisms and four studies investigating DNA methylation were included. Polymorphisms in the MTHFR, ABCB1, ABCC2, ABCG2, SLCO1B, miR-1206, miR-3683, CAT, and VDR genes were associated as risk factors for OM and polymorphisms in the TYMS and miR-4268 genes were associated as protective factors. With regard to DNA methylation, associations such as protection or susceptibility to OM have not yet been proven. However, studies have shown that DNMT1 methylation and hypomethylation in total DNA and in the TNF-α gene are associated with recovery of the oral mucosa. Conclusions: Genetic variants are associated with OM in various biological pathways, such as folate metabolism, transport proteins, epigenetic machinery, oxidative stress, and vitamin D metabolism. The DNA methylation profile, which is still poorly understood in the pathogenesis of OM, is associated with mucosal recovery (inflammation and epigenetic machinery). Genetic and epigenetic markers may be tools to indicate a patient’s susceptibility to developing OM, and epigenetic markers may be a target for therapies. Full article

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined use in high-risk statin-intolerant patients remains limited. Furthermore, the pharmacokinetics of statins in toxic concentrations are poorly characterized in clinical settings. Case Presentation: We present two cases of genetically confirmed statin-induced rhabdomyolysis, both accompanied by severe acute kidney injury requiring renal replacement therapy. In both patients, serial measurements of rosuvastatin plasma concentrations revealed markedly delayed elimination, with detectable levels persisting for several weeks despite ongoing dialysis. Estimated half-lives exceeded 7 days in both cases, far beyond the known therapeutic range. Genetic testing identified SLCO1B1, ABCB1, and CYP2C9 polymorphisms linked to reduced hepatic uptake and impaired drug clearance. Following biochemical recovery, both patients were initiated on a triple non-statin lipid-lowering regimen consisting of ezetimibe, bempedoic acid, and inclisiran. The combination was well tolerated, with no recurrence of muscle-related symptoms or biochemical toxicity. LDL-C levels were reduced from 3.05 to 1.59 mmol/L and from 4.99 to 1.52 mmol/L, respectively, with sustained response over 12 and 40 weeks. Full lipid profiles demonstrated favorable changes across all parameters. Conclusions: These two cases suggest that the combination of ezetimibe, inclisiran, and bempedoic acid may serve as a safe and effective therapeutic option in patients with severe statin intolerance. Pharmacogenetic testing and serial pharmacokinetic assessment may guide personalized lipid-lowering strategies and improve outcomes in this challenging patient population. Full article

Background: Neuralgic amyotrophy (NA), also known as Parsonage–Turner syndrome, brachial neuritis, and idiopathic brachial plexopathy, is a rare and potentially debilitating peripheral nerve disorder characterized by acute-onset shoulder pain followed by progressive motor deficits. It is often under-recognized, with an estimated incidence of 1 to 3 per 100,000 annually, though some studies suggest the actual prevalence may be significantly higher. The condition typically progresses through three phases, an acute painful phase, a phase of weakness, and a recovery phase, with sensory disturbances common in addition to motor weakness. The exact pathogenesis of NA remains unclear, though it is thought to involve a combination of genetic, environmental, and immunological factors. While neurologic complications following hematopoietic stem cell transplantation (HSCT), such as neuropathies and myopathies, have been documented, NA remains exceedingly rare in this context, with only a few reported cases. The pathophysiology in HSCT patients is hypothesized to involve immune dysregulation, graft-versus-host disease (GvHD), infection, and the effects of immunosuppressive therapy. Diagnosis is primarily clinical, supported by electrodiagnostic studies and MRI, though no laboratory markers exist. The management of NA is largely supportive and multimodal, focusing on pain control and rehabilitation. Objectives: The objective of this study was to describe the characteristics, clinical course, and outcomes of patients admitted for HSCT who were subsequently diagnosed with NA. Study Design: This retrospective case series from a single institution examined nine (N = 9) patients who developed acute shoulder pain following HSCT. We collected data on demographics, transplant details, clinical features, MRI findings, and electrodiagnostic studies, summarized using descriptive statistics. The diagnosis of neurologic amyotrophy was based on clinical presentation and corroborated by imaging and electrodiagnostic results. Long-term follow-up was assessed to evaluate symptom recovery. Results: Between August 2020 and July 2022, nine patients (44% male, median age 60) were diagnosed with NA following autologous (n = 4) or allogeneic (n = 5) HSCT. The onset of severe shoulder pain occurred at a median of 9 days post-transplant (range 1–21 days), with the majority of patients experiencing unilateral pain, predominantly affecting the right shoulder (55%). Neurologic weakness developed on average 5.1 days after pain onset, and sensory deficits were observed in all but one patient. MRI findings revealed muscle edema, atrophy, and enhancement in six patients, while electromyography confirmed NA in five. Due to the small sample size, statistical analyses, including p-values, confidence intervals, and trend comparisons, were not performed, and thus no conclusions can be drawn regarding associations between variables such as early onset and worse outcomes. Shoulder pain resolved after a median of 23 days (range 8–40 days). Long-term follow-up (>1 year) showed that three patients achieved full or near-full recovery, four partially recovered, and two showed minimal improvement. Conclusions: NA should be highly suspected in patients with acute shoulder pain and neurologic symptoms post-HSCT. To improve diagnostic accuracy and clinical outcomes, we recommend enhanced clinician awareness, the implementation of targeted diagnostic protocols (such as MRI and electrodiagnostic studies), and the establishment of standardized long-term follow-up protocols. Full article

Background: The marine bacterium Vibrio campbellii has been a model system for the study of bacterial quorum sensing and is increasingly recognized as a formidable aquatic animal pathogen. While genetically tractable, the study of this species in basic and applied research still relies upon laborious and time-consuming conjugation methods for plasmid DNA transformation. Methods: In this study, we developed an electroporation protocol using the most studied strain of this species, V. campbellii ATCC BAA-1116. An electroporation efficiency of up to 3 × 10⁴ CFU/μg DNA was demonstrated using derived parameters (10 kV/cm, 400 Ω, 25 μF), which took cell growth phase at harvest, plasmid DNA amount, and recovery conditions into account. The electroporation protocol was tested using several different plasmids and with additional strains of V. campbellii and sister species V. harveyi. Results: Interestingly, of the eight other V. campbellii strains tested, only three others, which also happened to be the three most recent environmental isolates with the fewest number of laboratory passages, were amenable to electroporation-mediated transformation. Conclusions: This electroporation protocol expands the tool set for studying V. campbellii and provides interesting insights into DNA transformation and uptake in this and related bacterial species. Full article

Background/Objectives: Human-driven selection has shaped modern horse breeds into highly specialized athletes, particularly in racing. Arabian horses, renowned for their endurance, provide an excellent model for studying molecular adaptations to exercise. This study aimed to identify genes commonly influenced by physical exertion in the gluteus medius muscle and whole blood of Arabian horses during their first year of race training. Methods: RNA sequencing of sixteen pure-breed Arabian horses was used to analyze transcriptomic changes at three key training stages. Differentially expressed genes (DEGs) were identified to explore their role in endurance and metabolic adaptation. Results: Seven genes—RCHY1, PIH1D1, IVD, FABP3, ANKRD2, USP13, and CRYAB—were consistently deregulated across tissues and training periods. These genes are involved in muscle remodeling, metabolism, oxidative stress response, and protein turnover. ANKRD2 was associated with mechanosensing and muscle adaptation, FABP3 with fatty acid metabolism, and USP13 with ubiquitination-related pathways crucial for muscle recovery and energy regulation. The transcriptomic overlap between muscle and blood suggests potential systemic biomarkers for athletic performance and endurance. Conclusions: Our findings highlight the importance of multi-tissue transcriptomic profiling in understanding exercise-induced molecular adaptations. The identified genes warrant further investigation as potential molecular markers for monitoring training progression and athletic potential in endurance horses. This study contributes to the growing field of equine sports genetics and may offer translational insights into human sports performance. Full article

The young mammalian central nervous system regenerates after spinal cord injury and recovers locomotion, whereas adult mice only show limited recovery that depends on the injury severity, genetic background, and physical therapy. At the molecular level, key regulators that contribute to recovery are cell adhesion molecules, such as L1CAM (L1). At the cell surface, L1 functions as a homotypic receptor that signal-transduces crucial functions in neuronal migration and survival, neurite outgrowth, myelination, formation of synapses, and synaptic plasticity. In the adult central nervous system, L1 is expressed only by neurons. We now show that L1 is unexpectedly also expressed by 26% microglia, freshly isolated from a 7-day-old mouse brain. At postnatal day 21, only 3% of microglia are L1-positive. Using a mouse mutant in which L1 is deleted specifically in monocytes of 10- to 14-week-old mice, functional recovery was reduced up to 4 weeks after injury at lower thoracic spinal levels. Also, NF200-immunoreactive and 5-HT-immunoreactive fibers were found decreased below the injury site as compared to wild-type mice. In conclusion, microglial cells that express L1 stimulate neurite outgrowth in vitro, improve functional recovery after spinal cord injury in adult mice, and increase fiber densities caudal to the lesion site. Full article

Maize is highly sensitive to water deficit but has high transpiration and biomass production, leading to a substantial water demand. Genetic engineering can overcome reproductive isolation and utilize drought-tolerant genes from distant species. Ammopiptanthus nanus is a relic of the Tertiary glaciation that can adapt to harsh environmental conditions. In our previous study, five maize homozygous T₈ lines overexpressing the AnVP1 gene from Ammopiptanthus nanus were generated and showed the enhancement of drought tolerance. However, the recipient inbred line Zh-1 was poor in yield and agronomic performance. In the present study, the AnVP1 gene was backcrossed from donor parent L10 (one of the five T₈ lines) into recurrent parent Chang 7-2 (one of the elite parents of the commercial hybrid Zhengdan 958). In total, 103 InDel markers were developed and used for assisted background selection. After two generations of foreground selection through glufosinate spraying, the detection of CP4 EPSP MAb1 strips, and the PCR amplification of the AnVP1 gene, along with the similarity of agronomic traits to the recurrent parent, and background selection assisted by these InDel markers, the transgenic AnVP1 gene became homozygous in the BC₂ lines. The average recovery rate of the genetic background of the recurrent parent reached 74.80% in the BC₁ population and 91.93% in the BC₂ population, respectively. The results of RT-PCR and RT-qPCR indicated the stable expression of the AnVP1 gene in the two ultimately selected BC₂F₃ lines, BC₂-36-12 and BC₂-5-15. The drought tolerance of these two BC₂F₃ lines were significantly improved compared to the recurrent parent Chang 7-2, as revealed by their wilting phenotype and survival rate of seedlings. This improvement was related to the enhancement of water-retention ability, as indicated by higher RWC and the reduction in damage, as shown by the decrease in REL, MDA, and H₂O₂ under drought stress. The result of field evaluation in two arid and semi-arid environments indicated that the drought tolerance of Chang 7-2 was significantly improved. This study suggests that the improved Chang 7-2 can be crossed with Zheng 58 to develop the transgenic commercial hybrid Zhengdan 958. Full article

Background/Objectives: Phosphine resistance in insects involves a complex interplay of genetic and physiological factors, which are often poorly understood. Resistance to high concentrations of phosphine worldwide poses a formidable challenge for stored-product pest management and affects global food security. Understanding the genetic basis of phosphine resistance in the red flour beetle, Tribolium castaneum, is urgent because of the species’ status as a notorious insect pest of stored grains and their resistance to major classes of insecticides. In this study, we take advantage of T. castaneum as a model species for biological and genetic studies. Methods: To tease apart genetic mutations and the differential expression of genes responding to phosphine intoxication, we set up 16 different exposure tests to compare the effects of phosphine dose, exposure time, and sampling time on gene expression in phosphine-susceptible and -resistant T. castaneum adults. Results: We examined the enrichment of gene ontology terms in genes that were differentially expressed and found that the data further distinguished differences in gene expression by insect strain, phosphine dose, exposure time, and recovery from phosphine exposure. The gene-encoding cytochrome P450 9e2 was expressed more in phosphine-resistant compared to phosphine-susceptible insects under all treatment conditions and was significantly higher in expression in resistant insects that were sampled after short or long phosphine exposures. Therefore, this gene may serve as a new phosphine resistance marker in T. castaneum and can further be utilized as a diagnostic tool for resistance detection. Conclusions: These data are important to understand the complex molecular changes in insects that have reduced sensitivity to phosphine to develop new monitoring and resistance prevention strategies. Full article

Background: Opuntia ficus-indica (OFI) cladodes are valuable and underestimated by-products that provide significant amounts of biologically active compounds. In this paper, microwave-assisted extraction (MAE) was performed for the recovery of phenolic compounds from OFI cladodes using two approaches: response surface methodology (RSM) and artificial neural network–genetic algorithm (ANN-GA), which were then compared following statistical indicators. Materials and Methods: Four independent factors were employed in the optimization process (solvent concentration, microwave power, irradiation time, and solid-to-liquid ratio) by selecting the total phenolic content (TPC), estimated by the Folin–Ciocalteu method, as a response. The optimized extract was tested for antioxidant capacity using the Folin–Ciocalteu reagent, Trolox Equivalent Antioxidant Capacity (TEAC), and oxygen radical absorbance capacity (ORAC) assays and for antimicrobial activity against 16 pathogenic strains using the agar well diffusion method. Results: The maximum TPC values predicted with maximizing desirability function for RSM were 2177.01 mg GAE/100 g DW and 1827.38 mg GAE/100 g DW for the ANN. Both models presented certain advantages and could be considered reliable tools for predictability and accuracy purposes. Using these conditions, the extract presented high antioxidant capacity for FCR assay (13.43 ± 0.62 mg GAE/g DW), TEAC (10.18 ± 0.47 µmol TE/g DW), and ORAC (205.47 ± 19.23 µmol TE/g DW). The antimicrobial activity of the optimized extract was pronounced only with respect to S. aureus alimentarius, Streptococcus, E. coli, P. aeruginosa, and A. flavus. Conclusions: This study underlines the high effectiveness of the optimization approaches in providing a maximum recovery of bioactive compounds from OFI cladodes to formulate food and pharmaceutical products with functional qualities. Full article

Background/Objectives: On 22 February 2021, a coastal landslide in Italy caused the collapse of an old cemetery, displacing approximately 370 coffins, with over 200 plunging into the sea. This disaster necessitated the recovery and identification of human remains under challenging conditions to provide closure to families and uphold the dignity of the deceased. Methods: Recovery operations involved firefighters and scuba divers, followed by forensic analysis conducted by the Medical Staff of Legal and Forensic Medicine. A post-mortem team utilized forms adapted from Interpol’s Disaster Victim Identification (DVI) standards to document remains, which included 140 decomposed bodies and 193 bags of commingled skeletal remains. DNA samples were collected from 147 bone fragments, primarily long bones and teeth, and compared with ante-mortem data gathered from relatives. Results: Of the 77 eligible relatives, 66 consented to DNA sample collection for genetic profiling, and 28 bodies were identified. Personal effects, clothing, medical devices, and a strong match between non-genetic AM and PM data led to an attribution of identity of other 19 individuals. Advanced post-mortem phenomena were observed in remains spanning from the late 19th century to 2017. An identification area at the cemetery facilitated streamlined operations, emphasizing environmental preservation and forensic accuracy. Conclusions: The cemetery collapse highlights the necessity for tailored forensic approaches in disaster scenarios. Accurate identification methods, combining genetic analysis and secondary means, are crucial for ensuring dignified burials and providing closure to affected families. Full article