In vivo investigation of the effects of light/dark cycle changes on synaptic plasticity in the dentate gyrus of the rat hippocampus

Aim: To investigate the impact of alterations in the light-dark cycle on the activity of dentate gyrus neurons within the hippocampus. Methods: The Light/Dark cycle was implemented in controlled environments equipped with automated lighting systems, maintaining a consistent 12-hour duration for each phase. Wistar Albino male rats were categorized into two groups. The light group was exposed to light from 08:00 to 20:00 followed by darkness, while the dark group remained in darkness from 08:00 to 20:00 and was exposed to light during the subsequent 12 hours. All periods were examined concurrently at the same time of day on the 30th experimental day. Results: There was no statistical difference in the slopes of excitatory postsynaptic potentials (EPSP) and the amplitudes of population spikes (PS) across varying stimulation intensities (p>0.05), with the exception of the 1.5 mA intensity (p=0.04). The stimulus facilitation index for the EPSP slope was significantly greater in the light group compared to the dark group at 120, 140, and 160 ms (p<0.05). The enhancement observed in the night group relative to baseline values during the PTP, induction, and maintenance periods was significantly lower than that in the light group (p<0.001). Conclusion: The results suggest that variations in light-dark frequency can influence the electrical characteristics of dentate gyrus neurons, indicating the presence of an endogenous timing mechanism within the hippocampus that may regulate hippocampal Long-Term Potentiation (LTP)

Investigation of some cytokine levels (IL-4, IL-5, IL-8, IL-12, and IL-33) in the sera of patients with cystic echinococcosis and fasciolosis

Aim: To evaluate serum levels of IL-4, IL-5, IL-8, IL-12p70, and IL-33 in patients with cystic echinococcosis and fascioliasis and to assess their diagnostic potential compared to healthy controls. Method: A total of 78 serum samples were analyzed, including 26 from patients with cystic echinococcosis, 26 from patients with fascioliasis, and 26 from healthy controls. Cytokine levels were measured using a multiplex ELISA assay, and intergroup comparisons were evaluated using IBM SPSS Statistics. Results: The echinococcosis group had significantly higher serum levels of IL-4, IL-5, IL-8, and IL-33 than the control group (p<0.05). Similarly, the fascioliasis group had significantly higher levels of IL-4, IL-5, and IL-8 than the control group (p<0.05), but no significant differences were observed for IL-33 and IL-12p70. Between the helminth groups, the echinococcosis group had significantly higher levels of IL-4 (p=0.003), IL-5 (p<0.001), and IL-33 (p=0.015) than the fascioliasis group. Conclusions: Cytokine profiles in helminth infections differ significantly from those in healthy controls and between parasite species. Th2-skewed responses, characterized by elevated IL-4 and IL-5 levels, were common, while IL-8 and IL-33 involvement suggests roles for both innate and adaptive immunity in disease pathogenesis. In echinococcosis, IL-33 may serve as a biomarker for early diagnosis, recurrence detection, and therapy monitoring, and it provides insights into the immune response to infections

Vortioxetine modulates Nrf2/HO-1 signaling and antioxidant defense in a cuprizone-induced demyelination model

Aim: To evaluate the effects of vortioxetine on oxidative stress and antioxidant defense responses through the regulation of the Nrf2/HO-1 signaling pathway in a mouse model of cuprizone-induced demyelination, representing experimental Multiple Sclerosis (MS). Method: Twenty-four male C57Bl/6 mice were randomly divided into four groups: control, cuprizone, cuprizone + vortioxetine, and vortioxetine. Demyelination was induced by administering cuprizone (10 mg/kg) via oral gavage every alternate day for a duration of 5 weeks. Vortioxetine (10 mg/kg) was delivered intraperitoneally to the appropriate groups for the same period. Biochemical analyses were conducted to assess nuclear and total Nrf2, HO-1, and total antioxidant status (TAS). Results: Cuprizone treatment led to a significant increase in HO-1 levels compared to the control group while co-administration with vortioxetine significantly reduced HO-1 levels relative to the cuprizone group. Nuclear Nrf2 expression was elevated in the cuprizone group and significantly decreased in the vortioxetine co-treatment group. The nuclear-to-total Nrf2 ratio was significantly lower in the co-treatment group compared to cuprizone group. TAS levels were significantly increased in both the cuprizone and cuprizone + vortioxetine groups relative to control, whereas TAS values in the vortioxetine group were significantly lower when compared to the co-treatment group and the cuprizone group. Conclusions: Vortioxetine effectively modulated the Nrf2/HO-1 pathway and reduced oxidative stress in a mouse model of demyelination. These findings suggest the potential of vortioxetine as a therapeutic agent for demyelinating diseases, such as MS

ABO incomplete antibodies for COVID-19

Aim: To investigate whether the infectivity of severe acute respiratory syndrome coronavirus 2 was affected by covering and hiding blood group antigens with incomplete ABO antibodies. Methods: Incomplete antibodies were produced with using animal and human monoclonal/polyclonal antiA and AntiB antibodies. The aforementioned antibodies were converted to incomplete ABO antibodies through the utilization our patented method. The aforementioned incomplete antibodies were then incubated with the coronavirus in cell cultures. Moreover toxicity and effect of these two type incomplete antibodies were calculated.  Results: Incomplete antibodies obtained from animals was highly toxic when encountered with severe acute respiratory syndrome coronavirus 2 in cell culture, the cells could not divide and the process could not be performed. However, the incomplete form of antibodies obtained from humans exhibited markedly reduced or even no toxicity when encountered with severe acute respiratory syndrome coronavirus 2. Even so, the study could be done with human originated incomplete antibodies, these incomplete antibodies were not effective against severe acute respiratory syndrome coronavirus 2, meaning they could not be used for treatment and prevention purposes for COVID-19. Conclusion: Human-derived incomplete antibodies did not completely eliminate the COVID-19 virus from infecting the cell, but slightly reduced it. Incomplete antibodies of animal origin are toxic to the cell. This study has shown that human-derived incomplete antibodies cannot currently be used as a treatment option for COVID-19, but since they are not toxic to the cell, and further studies can be carried out. The results of this study need to be supported by immunosuppressed animal studies

Evaluation of a central core MDR region as an optimum chromatin opening model

Aim: To examine whether the sub-regions of the HNRPA2B1 CBX3 UCOE (A2UCOE) preserved UCOE functionality. This inquiry was driven by several reports that challenge the requirement of associated promoter activity for UCOE functionality. Method: The 0.9kb central A2UCOE region, thought to form a potential MDR (methylation determining region), was placed upstream of the SFFV-eGFP cassette. These constructs were subsequently analyzed alongside the 1.5A2UCOE and 2.2A2UCOE to assess their ability to inhibit transcriptional repression. Results: In this study, we investigated whether sub-regions of the HNRPA2B1 CBX3 UCOE (A2UCOE) retained UCOE activity. Lentiviral vectors were used to evaluate the stability and efficiency of eGFP expression in P19 and F9 embryonal carcinoma cells. LB medium was prepared, and recombinant plasmids were transformed into competent E. coli DH5α cells. HEK293T cells were cultured for lentiviral production and transduction experiments were performed. eGFP expression was analyzed by flow cytometry before and after differentiation of P19 and F9 cells. Statistical analysis was performed using Prism, with p < 0.05 considered significant. Conclusions: This study demonstrates that the 0.9 kb core region of A2UCOE, containing the promoters of HNRPA2B1 and CBX3, exhibits partial resistance to transgene silencing in both undifferentiated and differentiated P19 and F9 cells. The findings indicate that the size of the CpG-rich region is critical for maintaining open chromatin structure and ensuring full UCOE functionality. Our study highlights the potential of smaller A2UCOE subregions for gene therapy; however, further optimization is required to achieve full activity independent of promoter influence

Investigation of the antitumoral activity of tarantula cubensis extract on human hepatocelular cancer cells

Aim: To investigate the antitumor effects of tarantula cubensis alcoholic extract (TCE) on the human hepatocellular cell line (HepG2). Methods: Various concentrations (1, 5, 10, 20, 50, 100, 250, and 500 µg/ml) of TCE were applied to HepG2 cells, which were then incubated for 24, 48, and 72 hours. Analysis was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Immunohistochemistry and apoptosis (Ki-67) analysis were conducted on cells treated with 1 and 5 µg/ml TCE for 24, 48, and 72 hours. Results: The most appropriate doses of TCE for the HepG2 cell line were found to be 5 µg/ml at 24 hours and 1 µg/ml at 48 and 72 hours. Ki-67 H-SCOR in HepG2 cells treated with TCE significantly decreased compared to the control group (p<0.001). Conclusion Our study suggests that TCE may alter normal cancer physiology by stimulating apoptosis in HepG2 cells via the Ki-67 pathway, leading to cell death. Therefore, TCE has the potential to provide a new perspective in the treatment of HCC

Choroidal characteristics in HIV infection and their association with disease severity

Aim: To evaluate choroidal characteristics in patients with Human Immunodeficiency Virus (HIV) using spectral-domain optical coherence tomography (SD-OCT), and assess their correlation with disease severity. Method: Fifty-eight eyes from 29 HIV-positive patients and 62 eyes from 31 age and sex-matched healthy controls were included. Measurements of choroidal thickness (CT), total choroidal area (TCA), stromal area (SA), and luminal area (LA) were obtained via SD-OCT (Maestro, Topcon Co., Tokyo, Japan). The choroidal vascular index (CVI) was calculated using the binarization method. Disease duration, highly active antiretroviral therapy (HAART) duration, HIV-RNA, and CD4 T cell count at diagnosis and at the time of examination, and venereal disease research laboratory (VDRL) test results were recorded. Correlations between SD-OCT results and HIV parameters were analyzed. Results: No significant differences in age or sex were observed between groups (p=0.988 and p=0.355, respectively). Although the HIV group had lower mean values for CT, TCA, LA, SA, and CVI than controls, these differences were not statistically significant (p=0.344, p=0.054, p=0.075, p=0.865, p=0.313, respectively). SA was inversely correlated with CD4 T cell counts (r = -0.477, p = 0.014). HAART duration was inversely correlated with CT (r=-0.376, p=0.044). VDRL positivity did not affect OCT parameters (p>0.05). Conclusions: Choroidal structures were thinner in patients who had been on HAART for a longer duration compared to those who were newly diagnosed. Changes in choroidal substructures may be more closely associated with long-term HIV infection or HAART duration rather than HIV-RNA or CD4 T cell counts

Comparison of neutrophil lymphocyte ratio and platelet lymphocyte ratio with Ranson criteria in acute biliary pancreatitis

Aim: To evaluate the diagnostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the severity of acute biliary pancreatitis, in comparison with the Ranson scoring system. Methods: A total of 353 patients diagnosed with acute biliary pancreatitis between January 2019 and December 2023 were retrospectively analyzed. Demographic data, laboratory findings, NLR, PLR, and Ranson scores were recorded. Patients were grouped as mild and severe according to clinical severity. The diagnostic performances of NLR, PLR, and Ranson score were assessed using receiver operating characteristic (ROC) curve analysis. Results: NLR, PLR, and Ranson scores were significantly higher in the severe pancreatitis group compared to the mild group (p<0.001 for all). ROC analysis revealed that Ranson score had the highest area under the curve (AUC = 0.85), followed by NLR (AUC = 0.82) and PLR (AUC = 0.75). Sensitivity and specificity values were acceptable for all three parameters in distinguishing severe disease. Conclusion: NLR and PLR are simple, cost-effective, and accessible inflammatory markers that may assist in predicting disease severity in acute biliary pancreatitis. Their diagnostic power is comparable to the Ranson scoring system and may support early risk stratification in clinical practice

Alcoholic neuropathy-associated changes in K+ conductance of primary dorsal root ganglion neurons

Aim: Alcohol-induced peripheral neuropathy (AIN) is a prevalent and debilitating condition, yet current knowledge of the molecular mechanisms is limited. In this study, we aimed to analyze the impact of chronic alcohol exposure on macroscopic K⁺ currents in dorsal root ganglion (DRG) neurons, providing insight into potential therapeutic targets for neuropathic pain. Methods: An AIN model was established in adult male Sprague-Dawley rats by administering 35% ethanol (10 g/kg, twice daily) for 10 weeks. Whole-cell patch-clamp methodology was applied to measure macroscopic outward K⁺ currents in the DRG. Depolarizing voltage steps (−60 to +100 mV, 10 mV increments) were applied to elicit K⁺ currents. Data were analyzed for current–voltage relationships, conductance–voltage curves, and steady-state activation parameters (maximum conductance, half-activation voltage V₁/₂, and slope factor k). Results: Electrophysiological recordings revealed that peak K⁺ current amplitudes in DRG neurons were significantly reduced in AIN rats (7.6 ± 0.7 nA) compared to controls (10.2 ± 0.7 nA, p < 0.05) at voltages between + 80 and + 100 mV. Maximum K⁺ conductance was also decreased in the AIN group (42.2 ± 3.9) versus controls (56.1 ± 4.1, p < 0.05). Additionally, V₁/₂ shifted leftward in AIN neurons (1.6 ± 1.9 mV) compared to controls (9.4 ± 2.1 mV), and the slope factor (k) modestly changed from 17.7 ± 1.2 to 20.7 ± 1.1. Conclusion: By elucidating a key ionic mechanism underlying alcohol-induced neuropathy, this study provides a strong foundation for the development of targeted pharmacotherapies aimed at restoring K⁺ channel function for AIN

Are the frequency and severity of COVID-19 infection higher in cancer patients than in the general population?

Aim: To investigate whether cancer increases the frequency and severity of coronavirus disease (COVID-19). Methods: A total of 641 cases were included in this study, comprising 425 cancer cases and 216 non-cancer cases. The non-cancer subjects were spouses and first-degree relatives of cancer patients, all residing in the same household as the cancer subjects included in the study. Results: In both the patient and the control groups, the history of COVID-19 infection and disease severity were evaluated. There was no statistically significant difference in the frequency of COVID-19 infection between cancer and control groups (30.3% vs. 24.6%, p = 0.133). Additionally, there was no statistically significant difference between metastatic and non-metastatic cancer cases regarding the frequency of COVID-19 infection (36% vs. 29%, p = 0.236). The frequency of COVID-19 infection was also comparable between vaccinated cancer patients and vaccinated control subjects (p = 0.108). No statistically significant difference was observed between the cancer patients and control groups in terms of disease severity among patients with COVID-19 (p = 0.406). Regression analysis showed that age ≥65 years and vaccination were significantly associated with a lower risk of COVID-19 infection. Cancer group and gender were not found to have an independent association with COVID-19 infection. Conclusion: This study found no difference in the frequency or severity of COVID-19 infection between the cancer and control group. Additionally, older age and vaccination were protective factors against COVID-19, while cancer status did not appear to affect the risk of infection