Pathophysiology

Acidosis and its associated pathologies predispose patients to develop cardiac arrhythmias and even cardiac arrest. These arrhythmias are assumed to be the result of membrane depolarization, however, the exact mechanism of depolarization during acidosis is not well defined. In our study, the model of quantum tunneling of protons is used to explain the membrane depolarization that occurs during acidosis. It is found that protons can tunnel through closed activation and inactivation gates of voltage-gated sodium channels Nav1.5 that are present in the membrane of cardiac cells. The quantum tunneling of protons results in quantum conductance, which is evaluated to assess its effect on membrane potential. The quantum conductance of extracellular protons is higher than that of intracellular protons. This predicts an inward quantum current of protons through the closed sodium channels. Additionally, the values of quantum conductance are influential and can depolarize the membrane potential according to the quantum version of the GHK equation. The quantum mechanism of depolarization is distinct from other mechanisms because the quantum model suggests that protons can directly depolarize the membrane potential, and not only through indirect effects as proposed by other mechanisms in the literature. Understanding the pathophysiology of arrhythmias mediated by depolarization during acidosis is crucial to treat and control them and to improve the overall clinical outcomes of patients. Full article

Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program. Full article

A mature teratoma is a germinal neoplasm that differentiates from embryonic multipotent cells into three germ layers. There may also be glandular tissue. The literature describes a total of 658 cases of ovarian neuroendocrine neoplasms, mainly in women over 40 years of age. The authors, together with a systemic review, present a case of a 16-year-old girl diagnosed with and treated for a neuroendocrine tumor. Case description: A 16-year-old girl visited the Paediatric Gynaecology Outpatient Clinic because of abdominal pains that intensified during menstruation. Standard painkillers and diastolic drugs were ineffective. An ultrasound examination revealed a large tumor with a heterogeneous structure in her right ovary. A sparing operation was carried out. During laparotomy, the lesion was enucleated, leaving healthy tissue. Histopathological examination revealed the typical features of teratoma, as well as the coexistence of a G1 neuroendocrine tumor. Immunohistochemical examination (IHC) showed the presence of markers characteristic for this type of tumor. The patient requires constant monitoring in the Endocrinology and Oncological Gynaecology Clinic. Conclusion: Tissue of neuroendocrine neoplasm within a teratoma is rare in this age group of patients; thus, there are currently no standards for long-term follow-up. This case adds to the body of evidence and demonstrates a possible good prognosis with non-aggressive behavior in G1 neuroendocrine tumors and teratomas in young patients. Full article

Wound healing is an important medical problem. We evaluated the efficacy of locally administered mesenchymal stem cells (MSCs) isolated from human umbilical cords on the dynamics of skin wound healing. The study was conducted on the backs of Wistar rats, where two square wounds were created by removing all layers of the skin. Four groups were studied in two series of experiments: (1) a Control_NaCl group (the wounds were injected with 0.9% NaCl solution) and a Control_0 group (intact wounds on the opposite side of the same rat’s back); (2) an MSC group (injected MSCs, local effect) and a Control_sc group (intact wounds on the opposite side of the back, remote MSC effect). The area and temperature of the wounds and the microcirculation of the wound edges were measured. Histological and morphometric studies were performed on days 3 and 7 after the wounds were created. The results showed that the injection trauma (Control_NaCl) slowed the regeneration process. In both MSC groups (unlike in either control group), we observed no increase in the area of the wounds; in addition, we observed inhibition of the inflammatory process and improved wound regeneration on days 1–3 in the remote group and days 1–5 in the local (injected) group. The MSC and Control_sc groups demonstrated improved microcirculation and suppression of leukocyte infiltration on day 3. On day 7, all the studied parameters of the wounds of the Control_0 group were the same as those of the wounds that received cell therapy, although in contrast to the results of the Control_ NaCl group, fibroblast proliferation was greater in the MSC and Control_sc groups. The dynamics of the size of the wounds were comparable for both local and remote application of MSCs. Thus, even a one-time application of MSCs was effective during the first 3–5 days after injury due to anti-inflammatory processes, which improved the regeneration process. Remote application of MSC, as opposed to direct injection, is advisable, especially in the case of multiple wounds, since the results were indistinguishable between the groups and injection trauma was shown to slow healing. Full article

Prostate cancer (PCa) progression is characterized by the emergence of resistance to androgen deprivation therapy (ADT). AKT/PKB has been directly implicated in PCa progression, often due to the loss of PTEN and activation of PI3K>PDK1>AKT signaling. However, the regulatory network of AKT remains incompletely defined. Here, we describe the functional significance of AKTIP in PCa cell growth. AKTIP, identified in an interactome analysis as a substrate of TLK1B (that itself is elevated following ADT), enhances the association of AKT with PDK1 and its phosphorylation at T308 and S473. The interaction between TLK1 and AKTIP led to AKTIP phosphorylation at T22 and S237. The inactivation of TLK1 led to reduced AKT phosphorylation, which was potentiated with AKTIP knockdown. The TLK1 inhibitor J54 inhibited the growth of the LNCaP cells attributed to reduced AKT activation. However, LNCaP cells that expressed constitutively active, membrane-enriched Myr-AKT (which is expected to be active, even in the absence of AKTIP) were also growth-inhibited with J54. This suggested that other pathways (like TLK1>NEK1>YAP) regulating proliferation are also suppressed and can mediate growth inhibition, despite compensation by Myr-AKT. Nonetheless, further investigation of the potential role of TLK1>AKTIP>AKT in suppressing apoptosis, and conversely its reversal with J54, is warranted. Full article

Decline in normal physiological pulmonary function has been attributed to premorbid conditions such as prehypertension. Research evidence suggests that physical activity reduces age-related decline in pulmonary function and improves the efficiency of the lungs in prehypertensive patients. However, there is a scarcity of data evidence relating to isometric exercise and pulmonary function. Furthermore, the interrelationship between the intensity and duration of isometric exercise and pulmonary function in these patients is still uncertain. Therefore, this study was undertaken to investigate the effect of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. To determine the effectiveness of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. A quasi experiment using a pre- and post-exercise method was carried out in two out-patients hospital settings. The sample comprised 192 sedentary pre-hypertensive subjects, aged between 30–50 years, that were randomly distributed into three groups of 64 participants each. The subjects performed, for 24 consecutive days, an isometric handgrip exercise at 30% Maximum Voluntary Contraction (M.V.C.). At the end of the 24 days, group one (GP1) discontinued, while group two (GP2) continued the exercise protocol for another 24 consecutive days and group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50% M.V.C. Determinants of lung function (outcomes) were Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), FEV1/FVC Ratio and Peak Expiratory Flow Rate (PEFR). The study shows that there was no statistically significant difference in the pre- and post-exercise outcomes for FEV1, FVC, FEV1/FVC Ratio and PEFR after 24 days for group 1. In group 2, there was a statistically significant difference in the FVC [(mean = 0.12 ± 0.12), (p = 0.002)], FEV1 [(mean = 0.15 ± 0.17), (p = 0.003)] and PEF [(mean = 0.85 ± 0.35), (p = 0.001)] after 48 days. In group 3, there was a statistically significant difference (p = 0.001) in all the outcomes assessed after 48 days. There was a between groups difference in favour of group 2 compared with group 1 for outcomes of FEV1 [(mean = 0.142 ± 0.68), (p = 0.005)] and PEF [(mean = 0.83 ± 0.19), (p = 0.0031)]. There was statistically significant difference in favour of group 3 compared to group 2, by increasing the exercise intensity from 30% to 50% M.V.C., for outcomes of FVC [mean change = 0.10 ± 0.052), (p = 0.005)], FEV1/FVC [mean change = 3.18 ± 0.75), (p = 0.017)] and PEF [(mean change = 0.86 ± 0.35), (p = 0.001)] after 48 days. Isometric handgrip exercise (after 48 days at 30% to 50% M.V.C.) improves outcomes of pulmonary function capacity in adults with prehypertension. Meanwhile, duration and/or increase in intensity of the isometric effort significantly contributed to the affects attained. Full article

A full understanding of the molecular mechanisms implicated in the etiopathogenesis of juvenile idiopathic arthritis (JIA) is lacking. A critical role for leukocyte proteolytic activity (e.g., elastase and cathepsin G) has been proposed. While leukocyte elastase’s (HLE) role has been documented, the potential contribution of proteinase 3 (PR3), a serine protease present in abundance in neutrophils, has not been evaluated. In this study we investigated: (1) PR3 concentrations in the synovial fluid of JIA patients using ELISA and (2) the cartilage degradation potential of PR3 by measuring the hydrolysis of fluorescently labeled collagen II in vitro. In parallel, concentrations and collagen II hydrolysis by HLE were assessed. Additionally, the levels of the co-secreted primary granule protein myeloperoxidase (MPO) were assessed in synovial fluid of patients diagnosed with JIA. We report the following levels of analytes in JIA synovial fluid: PR3—114 ± 100 ng/mL (mean ± SD), HLE—1272 ± 1219 ng/mL, and MPO—1129 ± 1659 ng/mL, with a very strong correlation between the PR3 and HLE concentrations (r_s = 0.898, p < 1 × 10^–6). Importantly, PR3 hydrolyzed fluorescently labeled collagen II as efficiently as HLE. Taken together, these novel findings suggest that PR3 (in addition to HLE) contributes to JIA-associated joint damage. Full article

The use of angiotensin-converting enzyme inhibitors (ACEis) has been reported to reduce symptoms of cognitive decline in patients with Alzheimer’s disease (AD). Yet, the protective role of ACEis against AD symptoms is still controversial. Here, we aimed at determining whether oral treatment with the ACEi lisinopril has beneficial effects on cognitive and physical functions in a Drosophila melanogaster model of AD that overexpresses the human amyloid precursor protein and the human β-site APP-cleaving enzyme in neurons. We found a significant impairment in learning and memory as well as in climbing ability in young AD flies compared to control flies. After evaluation of the kynurenine pathway of tryptophan metabolism, we also found that AD flies displayed a >30-fold increase in the levels of the neurotoxic 3-hydroxykynurenine (3-HK) in their heads. Furthermore, compared to control flies, AD flies had significantly higher levels of the reactive oxygen species (ROS) hydrogen peroxide in their muscle-enriched thoraces. Lisinopril significantly improved deficits in learning and memory and climbing ability in AD flies. The positive impact of lisinopril on physical function might be, in part, explained by a significant reduction in ROS levels in the thoraces of the lisinopril-fed AD flies. However, lisinopril did not affect the levels of 3-HK. In conclusion, our findings provide novel and relevant insights into the therapeutic potential of ACEis in a preclinical AD model. Full article

Hashimoto’s thyroiditis and psoriasis are inflammatory disorders that significantly impact patients’ quality of life, stressing the need for novel biomarkers of early diagnosis. This randomized clinical trial (NCT04693936) aims to identify Hashimoto’s thyroiditis’ and psoriasis’ metabolic biomarkers and to investigate the effect of environmental factors on the disease-related metabolic imprint and quality of life. Patients with Hashimoto’s thyroiditis, patients with psoriasis, and healthy individuals aged 18–60 will be recruited, enrolled according to eligibility criteria (medical history, clinical thyroid markers and the PASI score) and randomized to two groups. The intervention group will receive a combination of nutraceuticals for 6 months as part of a Mediterranean diet, and the control group will follow their usual diet. Data will be collected at baseline and the end of the study, including metabolite levels, lifestyle and anthropometric measurements, adherence to the Mediterranean diet (through the Mediterranean Diet Score) and disease-specific quality of life (through the Thyroid Patient Report Outcome for Hashimoto’s group, and the Dermatology Life Quality Index for the psoriasis group). This study will investigate metabolic biomarkers and related changes in Hashimoto’s thyroiditis and psoriasis and evaluate the association of metabolic changes with dietary factors and quality of life. Full article

Fetal undernutrition is a risk factor for cardiovascular diseases. Male offspring from rats exposed to undernutrition during gestation (MUN) exhibit oxidative stress during perinatal life and develop cardiac dysfunction in ageing. Angiotensin-II is implicated in oxidative stress-mediated cardiovascular fibrosis and remodeling, and lactation is a key developmental window. We aimed to assess if alterations in RAS during lactation participate in cardiac dysfunction associated with fetal undernutrition. Control dams received food ad libitum, and MUN had 50% nutrient restriction during the second half of gestation. Both dams were fed ad libitum during lactation, and male offspring were studied at weaning. We assessed: ventricular structure and function (echocardiography); blood pressure (intra-arterially, anesthetized rats); collagen content and intramyocardial artery structure (Sirius red, Masson Trichromic); myocardial and intramyocardial artery RAS receptors (immunohistochemistry); plasma angiotensin-II (ELISA) and TGF-β1 protein expression (Western Blot). Compared to Control, MUN offspring exhibited significantly higher plasma Angiotensin-II and a larger left ventricular mass, as well as larger intramyocardial artery media/lumen, interstitial collagen and perivascular collagen. In MUN hearts, TGF-β1 tended to be higher, and the end-diastolic diameter and E/A ratio were significantly lower with no differences in ejection fraction or blood pressure. In the myocardium, no differences between groups were detected in AT1, AT2 or Mas receptors, with MrgD being significantly lower in the MUN group. In intramyocardial arteries from MUN rats, AT1 and Mas receptors were significantly elevated, while AT2 and MrgD were lower compared to Control. Conclusions. In rats exposed to fetal undernutrition, RAS disbalance and associated cardiac remodeling during lactation may set the basis for later heart dysfunction. Full article

Saponins are steroidal or triterpenoid glycoside that is distinguished by the soap-forming nature. Different saponins have been characterized and purified and are gaining attention in cancer chemotherapy. Saponins possess high structural diversity, which is linked to the anticancer activities. Several studies have reported the role of saponins in cancer and the mechanism of actions, including cell-cycle arrest, antioxidant activity, cellular invasion inhibition, induction of apoptosis and autophagy. Despite the extensive research and significant anticancer effects of saponins, there are currently no known FDA-approved saponin-based anticancer drugs. This can be attributed to a number of limitations, including toxicities and drug-likeness properties. Recent studies have explored options such as combination therapy and drug delivery systems to ensure increased efficacy and decreased toxicity in saponin. This review discusses the current knowledge on different saponins, their anticancer activity and mechanisms of action, as well as promising research within the last two decades and recommendations for future studies. Full article

Limb girdle muscular dystrophy type R1 disease is a progressive disease that is caused by mutations in the CAPN3 gene and involves the extremity muscles of the hip and shoulder girdle. The CAPN3 protein has proteolytic and non-proteolytic properties. The functions of the CAPN3 protein that have been determined so far can be listed as remodeling and combining contractile proteins in the sarcomere with the substrates with which it interacts, controlling the Ca²⁺ flow in and out through the sarcoplasmic reticulum, and regulation of membrane repair and muscle regeneration. Even though there are several gene therapies, cellular therapies, and drug therapies, such as glucocorticoid treatment, AAV- mediated therapy, CRISPR-Cas9, induced pluripotent stem cells, MYO-029, and AMBMP, which are either in preclinical or clinical phases, or have been completed, there is no final cure. Inhibitors and small molecules (tauroursodeoxycholic acid, salubrinal, rapamycin, CDN1163, dwarf open reading frame) targeting ER stress factors that are thought to be effective in muscle loss can be considered potential therapy strategies. At present, little can be done to treat the progressive muscle wasting, loss of function, and premature mortality of patients with LGMDR1, and there is a pressing need for more research to develop potential therapies. Full article

Hepato-renal dysfunctions associated with hyperlipidemia necessitates a continuous search for natural remedies. This study thus evaluated the effect of dietary chitosan on diet-induced hyperlipidemia in rats. A total of 30 male Wistar rats (90 ± 10) g were randomly allotted into six (6) groups (n = 5): Normal diet, High-fat diet (HFD), and Normal diet + 5% chitosan. The three other groups received HFD, supplemented with 1%, 3%, and 5% of chitosan. The feeding lasted for 6 weeks, after which the rats were sacrificed. The liver and kidneys were harvested for analyses. Hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity, and renal biomarkers (ALT, AST, urea, and creatinine) were assayed spectrophotometrically. Additionally, expression of hepatic and renal CD43 and p53 was estimated immunohistochemically. The HFD group had elevated bodyweight compared to normal which was reversed in the chitosan-supplemented groups. Hyperlipidemia caused a significant (p < 0.05) decrease in the hepatic (AST, ALT, and ALP) and renal (AST and ALT) activities, while renal urea and creatinine increased. Furthermore, the HFD group showed an elevated level of hepatic and renal CD43 while p53 expression decreased. However, groups supplemented with chitosan showed improved hepatic and renal biomarkers, as well as corrected the aberrations in the expressions of p53 and CD43. Conclusively, dietary chitosan inclusion in the diet (between 3% and 5%) could effectively improve kidney and liver functionality via abatement of inflammatory responses. Full article

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health care emergency. Anti-SARS-CoV-2 serological profiling of critically ill COVID-19 patients was performed to determine their humoral response. Blood was collected from critically ill ICU patients, either COVID-19 positive (+) or COVID-19 negative (−), to measure anti-SARS-CoV-2 immunoglobulins: IgM; IgA; IgG; and Total Ig (combined IgM/IgA/IgG). Cohorts were similar, with the exception that COVID-19+ patients had a greater body mass indexes, developed bilateral pneumonias more frequently and suffered increased hypoxia when compared to COVID-19- patients (p < 0.05). The mortality rate for COVID-19+ patients was 50%. COVID-19 status could be determined by anti-SARS-CoV-2 serological responses with excellent classification accuracies on ICU day 1 (89%); ICU day 3 (96%); and ICU days 7 and 10 (100%). The importance of each Ig isotype for determining COVID-19 status on combined ICU days 1 and 3 was: Total Ig, 43%; IgM, 27%; IgA, 24% and IgG, 6%. Peak serological responses for each Ig isotype occurred on different ICU days (IgM day 13 > IgA day 17 > IgG persistently increased), with the Total Ig peaking at approximately ICU day 18. Those COVID-19+ patients who died had earlier or similar peaks in IgA and Total Ig in their ICU stay when compared to patients who survived (p < 0.005). Critically ill COVID-19 patients exhibit anti-SARS-CoV-2 serological responses, including those COVID-19 patients who ultimately died, suggesting that blunted serological responses did not contribute to mortality. Serological profiling of critically ill COVID-19 patients may aid disease surveillance, patient cohorting and help guide antibody therapies such as convalescent plasma. Full article

Increased neutrophil–endothelial binding and inflammatory responses are significant pathophysiological events in the maternal vascular system in preeclampsia, a hypertensive disorder in human pregnancy. Interleukin 6 (IL-6) and its soluble receptors (soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)) are critical inflammatory mediators. During pregnancy, maternal IL-6 and sgp130 levels were increased, but sIL-6R levels were decreased, in women with preeclampsia compared to normotensive pregnant women. However, little is known about differences in IL-6, sIL-6R, and sgp130 production by neutrophils and endothelial cells between normal pregnancy and preeclampsia. To study this, we isolated neutrophils and cultured human umbilical vein endothelial cells (HUVECs) from normal and preeclamptic pregnancies. Production of IL-6, sIL-6R, and sgp130 was measured. The role of placental factor(s)-mediated neutrophil production of IL-6, sIL-6R, and sgp130 was also determined by pretreating neutrophils with placental conditioned medium generated from placental villous cultures. We found that IL-6 and sgp130 were mainly produced by endothelial cells, while sIL-6R was mainly produced by neutrophils. Endothelial cells from preeclampsia produced significantly more IL-6 and sgp130, and neutrophils from preeclampsia produced significantly less sIL-6R than normal pregnancy cells. Interestingly, production of IL-6, sIL-6R, and sgp130 were time-dependently increased when neutrophils and endothelial cells were co-cultured. We also found that neutrophils from normal pregnancies produced more IL-6, but less sIL-6R, after being primed by preeclamptic-placental conditioned medium. These results demonstrated that neutrophils and endothelial cells have different capacities in producing IL-6, sIL-6R, and sgp130 between normal pregnancy and preeclampsia. These results also provide evidence that the placenta plays a role in inducing neutrophil activation in preeclampsia. Full article

Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. “Camone” tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress. Full article

Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction. Subsequent altered ion/fluid fluxes and/or signaling result in reduced cell migration and proliferation. Furthermore, the epithelial-mesenchymal transition appears to be partially triggered in CF, contributing to wound closure alteration. Finally, we pose our attention to diverse approaches to tackle this defect, discussing the therapeutic role of protease inhibitors, CFTR modulators and mesenchymal stem cells. Although the pathophysiology of wound repair in CF has been disclosed in some mechanisms, further studies are warranted to understand the cellular and molecular events in more details and to better address therapeutic interventions. Full article

Voltage-gated channels are crucial in action potential initiation and propagation and there are many diseases and disorders related to them. Additionally, the classical mechanics are the main mechanics used to describe the function of the voltage-gated channels and their related abnormalities. However, the quantum mechanics should be considered to unravel new aspects in the voltage-gated channels and resolve the problems and challenges that classical mechanics cannot solve. In the present study, the aim is to mathematically show that quantum mechanics can exhibit a powerful tendency to unveil novel electrical features in voltage-gated channels and be used as a promising tool to solve the problems and challenges in the pathophysiology of excitability-related diseases. The model of quantum tunneling of ions through the intracellular hydrophobic gate is used to evaluate the influence of membrane potential and gating free energy on the tunneling probability, single channel conductance, and quantum membrane conductance. This evaluation is mainly based on graphing the mathematical relationships between these variables. The obtained mathematical graphs showed that ions can achieve significant quantum membrane conductance, which can affect the resting membrane potential and the excitability of cells. In the present work, quantum mechanics reveals original electrical properties associated with voltage-gated channels and introduces new insights and implications into the pathophysiology of excitability- related disorders. In addition, the present work sets a mathematical and theoretical framework that can be utilized to conduct experimental studies in order to explore the quantum aspects of voltage-gated channels and the quantum bioelectrical property of biological membranes. Full article

Echis ocellatus snakebite causes more fatalities than all other African snake species combined. Moringa oleifera reportedly possesses an antivenom property. Therefore, we evaluated the effectiveness of M. oleifera ethanol extract (MOE) against E. ocellatus venom (EOV) toxicities. Thirty male rats were grouped as follows (n = 5): Group 1 (normal control received saline), groups 2 to 6 were administered intraperitoneally, 0.22 mg/kg (LD50) of EOV. Group 2 was left untreated while group 3 to 6 were treated post-envenoming with 0.2 mL of polyvalent antivenom, 200, 400, and 600 mg/kg of MOE respectively. MOE significantly (p < 0.05) normalized the altered haematological indices and blood electrolytes profiles. MOE attenuated venom-induced cellular dysfunctions, characterized by a significant increase in NRF2, and concomitant downregulation of increased antioxidant enzymes (SOD and CAT) activities in the serum and heart of the treated rats. MOE normalized the elevated TNF-α and IL-1β in serum and heart tissues. Furthermore, the IgG titre value was significantly (p < 0.5) higher in the envenomed untreated group compared to the MOE-treated groups. Hemorrhagic, hemolytic and coagulant activities of the venom were strongly inhibited by the MOE dose, dependently. Lesions noticed on tissues of vital organs of untreated rats were abolished by MOE. Our findings substantiate the effectiveness of MOE as a potential remedy against EOV toxicities. Full article