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Alzheimer's disease is a chronic complex neurodegenerative disease characterized with amyloid plaques and loss of neurons. TGF-β1 is important growth factor, plays critical roles in cell metabolism, tissue homeostasis, neuronal development, and synaptic plasticity. In this study, we aimed to examine the effect of TGF-β1 on the regulation of α, β, and γ-secretase enzymes, Aβ-40 accumulation, apoptosis, and neuronal damage in an experimental Scopolamine-induced AD-like model. The subjects were divided into 5 groups such as control, sham, TGF-β1 control, Scopolamin group, TGF-β1 treatment groups.Then all groups were divided into 2 subgroups according to 28th-56th days. Except for Morris water maze (MWM) test, hippocampus and prefrontal cortex tissues were taken for light-electron microscopic, immunohistochemical, and biochemical examinations. It was observed that learning and memory abilities, which decreased in the MWM test of the Scopolamine group, increased in the treatment groups. In addition, α-secretase expression decreased in the Scopolamin group, while it increased in the TGF-β1 treatment group. It was determined that Aβ-40 and caspase-3 immunoreactivity, β and γ-secretase enzyme levels increased in the Scopolamin group and decreased in TGF-β1 treatment group. Cellular degenerations were relatively decreased in TGF-β1 treatment group. It was thought that TGF-β1 might have a therapeutic effect on Alzheimer's disease by increasing memory performance and preventing Aβ-40 accumulation in the AD-like model induced by Scopolamine and also, may be effective preventing neuronal damage by down-regulating caspase-3 expression. When all the findings evaluated together, it was concluded that TGF-β1 could be evaluated as a therapeutic agent in Alzheimer's disease., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that affects the joints of approximately 1 % of the population worldwide and is seen 2-4 times less in males. INSL3 is a gender-specific peptide hormone produced much higher in males than in females and may have an anti-inflammatory role in RA. So, in this study, it was aimed to determine the possible anti-inflammatory effect and dose of insulin-like factor-3(INSL3) in an experimental Complete Freund's adjuvant(CFA)-induced RA male rat model and lipopolysaccharide(LPS)-induced macrophage cell line and compare it with prednisolone therapy. For in vivo experiments, 48 male mice were randomly divided into 6 groups with 8 subjects in each group: Control group, Arthritis group, Arthritis + Prednisolone(10 mg/kg) group, Arthritis + INSL3(0.08-0.8-8 μg/day) groups. Joint tissue samples obtained from sacrificed subjects were examined by histochemical and immunohistochemically methods after biometric analyses, arthritis severity scoring, and thermal latency experiments. LPS-induced macrophage cells were also treated with prednisolone(1 µg/ml) and INSL3(50-100-200 nM). Cell viability, cell morphology, and TNF-α and IL-6 immune reactivity were evaluated. According to the data obtained from in vivo analyses, it was seen that INSL3 reduced the paw diameter and arthritis severity scoring, degenerative changes, and inflammation and increased the thermal latency, compared to the arthritis group, although not as much as the prednisolone treatment group. In vitro analyses showed that high doses of INSL3 had positive effects on cell viability, morphology, TNF-α, and IL-6 immune reactivity. In conclusion, it was determined that the anti-inflammatory effect of INSL3 was not as pronounced as prednisolone, but it had a more favorable impact on macrophage cell viability and morphology. It was concluded that INSL3 may be a protective therapeutic agent in combination with existing treatment protocols in treating many autoimmune diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gulfidan Coskun reports financial support was provided by Cukurova University Faculty of Medicine. Gulfidan Coskun reports a relationship with Cukurova University Faculty of Medicine that includes: employment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: Inflammasome NLR family pyrin domain-containing 3 (NLRP3) is associated with neurological disorders. Neuroinflammation can be suppressed by inhibiting NLRP3 inflammasome activation, decreasing neurodegenerative disorder progression. We devised a therapeutic technique that can reduce neuroinflammation induced by microglial activation, avoiding neurodegeneration. We aimed to investigate the mechanisms underlying the pharmacological effects of galantamine and wedelolactone by evaluating the response of the nuclear factor kappa B (NF-κB) signaling pathway and NLRP3 inflammasome in lipopolysaccharide (LPS)-activated N9 microglia., Methods: LPS and adenosine triphosphate were used to activate the NLRP3 inflammasome in N9 microglial cells, which were pretreated with galantamine and wedelolactone. Caspase-1, NLRP3, NF-κB, and interleukin (IL)-1β levels were measured using RT-qPCR and immunostaining., Results: Combined administration of galantamine and wedelolactone rescued microglial cells from LPS-induced cell death. Furthermore, treatment with galantamine and wedelolactone led to the suppression of NF-κB expression. NLRP3, caspase-1, and IL-1β levels were decreased by the combined treatment., Discussion and Conclusion: The concurrent administration of galantamine and wedelolactone effectively suppresses the production of inflammatory cytokines and NLRP3 inflammasome activation in microglia. This inhibitory effect is likely linked to the NF-κB signaling pathway modulation. Therefore, this combined treatment is a potential therapeutic approach for neuroinflammatory diseases.

Endometriosis is a common gynecological hurting disorder in which tissue is similar to the tissue that normally lines the inner layer of the uterus. It often causes fertility problems. Unfortunately, effective treatments are limited. Therefore it's important to explore an imperative and easily accessible treatment to alleviate the probable pathologies and preserve fertility in endometriosis. Consequently, we aimed to investigate the effects of metformin, letrozole, and atorvastatin on inflammation and apoptosis in experimentally induced ovarian and peritoneal endometriosis in rat models. In the present study, 35 rats were randomly divided into five groups. Group 1: sham-operated control group. Group 2: untreated endometriosis group. Group 3: given 100 mg/kg/day of oral metformin. Group 4: given 0.1 mg/kg/day of oral letrozole. Group 5: given 2.5 mg/kg/day of oral atorvastatin. At the end of the 28 days, we examined Ki67, Bax and Bcl-2 immunoexpressions in ovarian and peritoneal tissues, and IL-6, IL-8, and TNF-α levels were evaluated from the peritoneal fluid. All medical treatment groups showed a significant decrease in Ki67 expression. A significant increase in Bax expression was also observed in all samples from all medical treatment groups (other than the untreated endometriosis groups). Further, a significant decrease in Bcl-2 expression was found in all medical treatment groups. IL-6, IL-8, and TNF-α levels were significantly lower in all medical treatment groups than in the endometriosis groups. In conclusion; Metformin, letrozole, and atorvastatin showed apoptosis induction and anti-inflammatory effects on both ovarian and peritoneal endometriosis in experimental models., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Functional disorders of the glymphatic system and Aquaporin-4 (AQP-4) channels take part in the pathophysiology of neurodegenerative disease. The aim of this study was to describe the distribution of AQP-4 channels in the prefrontal cortex and hippocampus in a mouse model of NMDA receptor blocking agent-induced schizophrenia-like behavior model. NMDA receptor antagonist MK-801 was used to produce the experimental schizophrenia model. MK-801 injections were administered for eleven days to Balb/c mice intraperitoneally. Beginning from the sixth day of injection, the spatial learning and memory of the mice were tested by the Morris water maze (MWM) task. A group of mice was injected with MK-801 for ten days without the MWM task. Hippocampus and prefrontal specimens were collected from this group. Tissue samples were stained immunohistochemically and AQP-4 channels were examined by electron microscope. Time to find the platform was significantly longer at MK-801 injected group than the control group at the MWM task. Also, time spent at the target quadrant by the MK-801 group was shorter compared to the control group. AQP-4 expression increased significantly at MK-801 group glial cells, neuronal perikaryon, perineuronal and pericapillary spaces. In the MK-801 group, there was remarkable damage in neurons and glial cells. Increased AQP-4 channel expression and neurodegeneration at the MK-801 group induced with schizophrenia-like behavior model. MK-801 induced NMDA receptor blockade causes a decline in cognitive and memory functions. Increased AQP-4 expression at the prefrontal cortex and hippocampus to elicit and transport products of synaptic neurotransmitters and end metabolites is suggested.

Mental retardation and hypotonia are found in virtually all Down syndrome (DS) individuals, whereas congenital heart defects (CHDs) are only present in a subset of cases. Although there have been numerous reports of the frequency of CHDs in DS, few of the studies have had complete ascertainment of DS in a defined geographic area. The Atlanta Down Syndrome Project, a population-based study of infants born with trisomy 21, provides such a resource. In the first 6.5 years of the study, 243 trisomy 21 livebirths were identified in the five-county Atlanta area (birth prevalence: 9.6/10,000). Cardiac diagnoses were available on 227 (93%) of the cases and 89% of these evaluations were made by echocardiography, cardiac catheterization, surgery, or autopsy. Of the 227 DS infants, 44% had CHDs including 45% atrioventricular septal defect (with or without other CHDs), 35% ventricular septal defect (with or without other CHDs), 8% isolated secundum atrial septal defect, 7%, isolated persistent patent ductus arteriosus, 4% isolated tetralogy of Fallot, and 1% other. This report is unique in that it contains the largest number of trisomy 21 infants ascertained in a population-based study where modern techniques for diagnosing cardiac abnormalities predominate.

Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non-disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.

Management of cardiogenic shock following neonatal myocardial infarction (MI) has received little attention in the literature. Advances in medical support have been pharmacologic in nature, yet the outcome remains dismal. We report the course of a neonate after MI. Extracorporeal membrane oxygenation was utilized for hemodynamic support during the immediate post-MI period. The patient initially was in massive cardiogenic shock, but her myocardial function recovered completely. She has a normal neurodevelopmental outcome at 22 months of age.

The cause of non-disjunction of chromosome 21 remains largely unknown. Advanced maternal age is associated with both maternal meiosis I (MI) and meiosis II (MII) non-disjunction events. While reduced genetic recombination has been demonstrated in maternal MI errors, the basis for MII errors remains uncertain. We studied 133 trisomy 21 cases with maternal MII errors to test the hypothesis that segregation at MII may also be influenced by genetic recombination. Our data support a highly significant association: MII non-disjunction involves increased recombination that is largely restricted to proximal 21q. Thus, while absence of a proximal recombination appears to predispose to non-disjunction in MI, the presence of a proximal exchange predisposes to non-disjunction in MII. These findings profoundly affect our understanding of trisomy 21 as they suggest that virtually all maternal non-disjunction results from events occurring in meiosis I.

Sucrose density centrifugation has been used to characterize the relative levels of AChE molecular forms in different parts of the brain, during development, or in various disease states. We have examined the influence of various tissue or sample storage and handling techniques on the abundance of the 4S and 10S molecular forms of AChE in rat forebrain. Our results demonstrate that freezing either a subcellular fraction or the intact tissue causes dramatic shifts in the level of the 4S and 10S molecular forms as compared to the values obtained in fresh tissue. Total AChE activity was unchanged suggesting that 4S and 10S forms are equally active and that 4S AChE is easily dissociated from 10S. These observations suggest that 4S and 10S molecular forms in brain are extremely labile and that great care should be taken when studying the factors that regulate these forms.