Neurochemical Journal最新文献

Abstract

This study aimed to explore the efficacy and safety of alteplase combined with urinarykallid for the intravenous thrombolysis of patients with acute cerebral infarction. Patients (n = 125) who were admitted to our hospital were included and divided into Group A (n = 60) and Group B (n = 65). Patients in Group A were treated with alteplase for intravenous thrombolysis, based on which urinarykallid was administered to patients in Group B as a combination treatment. Compared to Group A, Group B was significantly lower in hs-CRP and TNF-α levels (p < 0.001), total incidence of adverse reactions (p < 0.05), and NIHSS score (p < 0.001) and higher in IL-10 level (p < 0.001), total effective rate (markedly effective + effective/total cases × 100%. Compared to the single administration of alteplase, the combination of alteplase and urinarykallid for the intravenous thrombolysis of patients with acute cerebral infarction can achieve better efficacy at a lower incidence of adverse reactions and play a more significant role in clinical treatment.

Abstract—In 70 examined patients, 34 with the first psychotic episode (FPE) and 36 with chronic schizophrenia (CS), we studied dynamics of the prolactin (PRL), thyroid-stimulating hormone (TSH), and free thyroxine (T₄) during olanzapine therapy. Background hyperprolactinemia (HP) was observed in 52.9% of patients with FPE, which had with mean values of 971.1 ± 420 mIU/L, and in 50% of patients with CS (mean prolactin values were 1131 ± 845.4 mIU/L). In 11.8% of patients with FPE and in 16.6% of patients with CS, the level of free T₄ was below the standard values (mean values: 7.5 ± 0.3 pmol/L and 8.0 ± 0.8 pmol/L, respectively). TSH parameters in patients with FPE were within the reference values. Elevated background levels of TSH in patients with CS were observed in 11.1% of cases (4.8 ± 0.7 mIU/mL). By 6–8 weeks, an increase in mean PRL values was observed in all patients. Fluctuations in thyroid hormone levels by the end of therapy were insignificant. Four variants of dynamic changes in PRL and hypothalamic-pituitary-thyroid (HPT) axis hormones in patients during olanzapine therapy were identified. The relationship between PRL and thyroid hormones is discussed. The data obtained dictate the need to study the characteristics of the ratio of the levels of these hormones before the start of antipsychotic therapy (AT) in order to detect hypothyroidism and HP early, as well as to prevent the development of these hormonal dysfunctions in the process of AT and confirm the need to assess the levels of PRL and HPT-axis hormones in patients with FPE and CS before the start of the appointment of AT.

Abstract

Inhaled anesthetic sevoflurane is widely reported to induce neurotoxicity, whereas the underlying mechanism is less elucidated. Here, we investigated that sevoflurane anesthesia causes a decrease in learning and memory functions, especially in aged mice. BRCA1 was found to be downregulated by sevoflurane administration in the hippocampus. Sevoflurane exposure led to decreased BRCA1 in vitro, accompanied by an increase of β-amyloid precursor protein and β-amyloid. Aβ1-42 suppressed the protein abundance of BRCA1 but not mRNA, and BRCA1 could not alter the expression of β-amyloid. Furthermore, BRCA1 was observed to participate in the neurotoxicity induced by sevoflurane, since BRCA1 knockdown exacerbated, while overexpression mitigated sevoflurane-induced decrease of cell viability of neuronal cells. Our results demonstrated for the first time that the vital role of BRCA1 in sevoflurane-induced neurotoxicity, and β‑amyloid might serve as the link between BRCA1 and sevoflurane.

Abstract

Ciliary neurotrophic factor (CNTF) is a pluripotent neurotrophic factor with a high neuroprotective potential, a neurocytokine that has shown potential in therapy of neurodegenerative, mental and metabolic diseases. Pre-clinical data support the general concept of its promising survival and trophic effects, while recent clinical data support the theoretical role of CNTF for treating neurodegeneration and obesity. The data of occasional studies on CNTF levels in invasive (blood) and non-invasive (tears) human biomaterial suggest its potential use as a biomarker of selected brain diseases, though additional studies should be performed to validate it.

Abstract—Many individuals with schizophrenia also suffer from metabolic syndrome (MetS), which is a major risk factor for the development of cardiovascular disroders associated with a heavy burden of disease, as well as with premature death of patients. This study investigated the expression of 7 genes potentially important for the development of metabolic syndrome. QuantiGene Plex 2.0 technology was used to measure how 7 studied genes (DRD3, GHRL, FTO, LEPR, INSIG2, GSTP1, and ABCB1 (MDR1)) were expressed in leukocytes in 60 recently admitted patients with schizophrenia who had been on treatment with antipsychotic drugs. The preliminary results of our study show a change in the expression of the FTO gene in schizophrenic males with metabolic disorders, however, further studies are needed to determine the role of disturbances in the expression of this gene in the development of the metabolic syndrome in patients with schizophrenia.

Abstract

Beta-amyloid peptides (Aβ) are common risk factors associated with cognitive impairment, neuroinflammation, and apoptosis in Alzheimer’s disease (AD). The glycolytic enzyme PKM2 is an essential antioxidant intermediate by promoting glutathione (GSH) biosynthesis, shielding neurons against oxidative damage, and conferring neuroprotective effects. However, its role in AD has rarely been reported. This study aimed to explore the mechanism underlying PKM2 activation in an AD cell model via the PKM2 activator TEPP-46. Aβ administration in SH-SY5Y cells reduced cell viability while increasing inflammation, apoptosis, and oxidative disorder. PKM2 activity, rather than its expression, was reduced in the AD cell model. TEPP-46 administration could restore PKM2 activity, reverse the suppressive effect of Aβ on cell viability and proliferation, reduce the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), decrease Aβ-triggered cell apoptosis, and restore cellular oxidative stress. Furthermore, the effect of TEPP-46 on the AD cell model was confirmed by deactivating P62, reversing the Bax/Bcl-2 ratio, and activating the Nrf2/HO-1 pathway by western blotting. Additionally, colivelin, an Nrf2 antagonist, deactivates the Nrf2/HO-1 pathway and recovers oxidative stress. Colivelin administration could also offset the influence of TEPP-46 on Aβ-induced SH-SY5Y cell inflammation and apoptosis and viability.

Abstract

This study aimed to explore the amelioration of immune function and clinical symptoms in epilepsy patients following the implementation of topiramate therapy. We retrospectively analyzed 90 epilepsy patients treated at our institution from September 2020 to July 2022, segregating them into two groups: the observation group (n = 50, administered with a combination of carbamazepine and topiramate), and the control group (n = 40, treated with carbamazepine alone). The study evaluated disparities in clinical outcomes, immune function modifications, epilepsy score variances, quality of life indices, and incidence of adverse reactions before and after treatment in both groups. The observation group demonstrated a total treatment efficacy rate of 94.00% (47/50), significantly exceeding that of the control group, which stood at 75.00% (30/40) (P < 0.05). Pre-treatment epilepsy and QOLIE-31 scores showed no statistically meaningful difference between the two groups (P > 0.05); however, post-treatment evaluation after 3 months indicated that the observation group had significantly lower epilepsy scores and notably higher QOLIE-31 scores (P < 0.05). Although pre-treatment immune function indices (including CD3+, CD4+, and IgA levels) did not show a significant difference between the groups (P > 0.05), post-treatment levels of CD3+ and CD4+ were markedly higher, and IgA levels were lower in the observation group (P < 0.05). The observation group also exhibited a reduced overall incidence of adverse reactions (12.00%, 6/50), significantly lower than the control group (32.50%, 13/40) (P < 0.05). The adjunctive use of topiramate with standard therapy can enhance the clinical efficacy in epilepsy patients, ameliorating immune function, augmenting the quality of life, and escalating treatment safety, thereby presenting substantial value for clinical application.

Abstract

This review presents data from multilateral studies, aimed at determining the localization, release and the function of the cardioactive hormones found by acad. A. Galoyan and colleagues in the hypothalamic-pituitary system of the bovine brain. The isolated protein-carriers of the neurohormones K, C and G (PCK, PCC, PCG) have been found to differ from the protein-carrier of the vasopressin and oxytocin neurophysin. The coronary-dilating factors were also isolated from the bovine heart and medulla of the adrenal gland. Later, in various regions of the intact rat brain, PCG was immunohistochemically detected in the glial and nerve cells, as well as in the varicose nerve fibers and synaptosomes. In the intact rat heart, PCG was localized in the nerve fibers, as well as in the small catecholamine-containing SIF cells. Fourteen days after the unilateral vagotomy, aimed at clarifying the origin of PCG-IR in the heart, some PCG-Ir nerve fibers around the cardiomyocytes and the ganglion cells were detected mainly due to the preserved SIF cells and SCG sympathetic neurons containing PCG. PCG-immunonegative cardiac ganglion cells in both intact and colchicine-treated rats were excluded as a possible source of the external PCG-IR. Thus, PCG, together with the other neuropeptides studied by us (NPY, CGRP and VIP, SP, LENK) present in SIF cells, can be involved in the local regulatory mechanisms of the heart, thereby confirming the idea proposed by A. Galoyan regarding the “neurosecretion of the heart” and the literature data on the existence of the peptidergic system of the heart.

Abstract—Coordinated regulation of energy conversion processes in the brain maintains its highly productive work and efficient mental activity. Impairments of the brain energy metabolism are considered among pathogenetic factors in the schizophrenia origin, but presently it is difficult to say whether these impairments are primary and causative for the development of the disease or represent consequences of certain changes in the functioning of neurotransmitter and other neurochemical systems. This review discusses the main results of the energy metabolism research in schizophrenia–at various levels and using different approaches, as well as regards some attempts of influencing the energy processes in the brain as an adjunctive therapy in schizophrenia. To date, the efficacy of these therapeutic approaches has not been proven, this may be due to the paucity of studies and the lack of preliminary identification/stratification of patient subgroups to whom the energy metabolism-targeted therapy would be the most useful. Based on the data presented, one can conclude that an analysis is necessary of relationships between the psychopathological manifestations of schizophrenia and energy metabolism deviations for further identification of those patients to whom the use of mitochondrial modulators, mitoprotection, and other approaches may represent a promising method of adjunctive therapy.

Abstract

Hemorphins are a family of endogenous atypical opioid peptides released during the sequential cleavage of hemoglobin β-chain. Hemorphins are widely distributed in the organism and are implicated in pathophysiology of several diseases, including diabetes, cancer, Alzheimer disease and others. These peptides were identified several decades ago and their diverse therapeutic effects have been revealed. However, the exact molecular mechanisms involved in synthesis, metabolism and therapeutic effect of hemorphins are not fully understood. In this review, the current knowledge of hemorphins, focusing on their biological activity and Ca²⁺/CaM/CN-signaling pathway, involved in mechanisms of hemophins action is briefly summarized. These peptides have been intensively investigated at the Institute of Biochemistry (Armenia), and fundamental results are thoroughly discussed in this review.