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1.
Pathol Res Pract ; 258: 155320, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38728794

RESUMO

The objective of this study to examine the effects of curcumin and gallic acid use against oxidative stress damage in the autologous intraperitoneal ovarian transplantation model created in rats on ovarian follicle reserve, ovarian surface epithelium, and oxidant-antioxidant systems. 42 adult female Sprague Dawley rats (n=7) were allocated into 6 groups. Group 1 served as the control. In Group 2, rats underwent ovarian transplantation (TR) to their peritoneal walls. Group 3 received corn oil (CO) (0.5 ml/day) one day before and 14 days after transplantation. Group 4 was administered curcumin (CUR) (100 mg/kg/day), Group 5 received gallic acid (GA) (20 mg/kg/day), and Group 6 was treated with a combination of curcumin and gallic acid via oral gavage after transplantation. Rats were sacrificed on the 14th postoperative day, and blood along with ovaries were collected for analysis. The removed ovaries were analyzed at light microscopic, fluorescence microscopic, and biochemical levels. In Group 2 and Group 3, while serum and tissue Total Oxidant Levels (TOS) and Oxidative Stress Index (OSI) increased, serum Total Antioxidant Levels (TAS) decreased statistically significantly (p˂0.05) compared to the other groups (Groups 1, 4, 5, and 6). The ovarian follicle reserve was preserved and the changes in the ovarian surface epithelium and histopathological findings were reduced in the antioxidant-treated groups (Groups 4, 5, and 6). In addition, immunofluorescence examination revealed that the expression of Cytochrome C and Caspase 3 was stronger and Ki-67 was weaker in Groups 2 and 3, in comparison to the groups that were given antioxidants. It can be said that curcumin and gallic acid have a histological and biochemical protective effect against ischemia-reperfusion injury due to ovarian transplantation, and this effect is stronger when these two antioxidants are applied together compared to individual use.


Assuntos
Antioxidantes , Curcumina , Ácido Gálico , Folículo Ovariano , Reserva Ovariana , Ovário , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Feminino , Ácido Gálico/farmacologia , Curcumina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/patologia , Ovário/metabolismo , Ratos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Reserva Ovariana/efeitos dos fármacos , Antioxidantes/farmacologia , Epitélio/efeitos dos fármacos , Epitélio/patologia , Epitélio/metabolismo , Transplante Autólogo , Sinergismo Farmacológico
2.
Pathol Res Pract ; 252: 154948, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37977034

RESUMO

Lung cancer, known for its high mortality rates and poor prognosis, remains one of the most prevalent cancer types. Early detection and effective treatment methods are crucial for improving survival rates. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. Long non-coding RNAs (lncRNAs), which play vital roles in various biological processes, have been implicated in the development of cancer and can impact key therapeutic targets in different cancer types. In NSCLC, the dysregulation of specific lncRNAs, such as MALAT1 and NORAD, has been associated with neoplastic initiation, progression, metastasis, tumor angiogenesis, chemoresistance, and genomic instability. Both MALAT1 and NORAD directly regulate the expression of the transcription factor E2F1, thereby influencing cell cycle progression. Additionally, MALAT1 has been reported to affect the expression of p53 target genes, leading to cell cycle progression through the repression of p53 promoter activity. NORAD, on the other hand, is indirectly regulated by p53. The AT-rich interaction domain (ARID) family of DNA-binding proteins, particularly ARID3A and ARID3B, are involved in various biological processes such as cell proliferation, differentiation, and development. They also play significant roles in E2F-dependent transcription and are transcriptional targets of p53. The intricate balance between promoting cellular proliferation through the pRB-E2F pathway and inducing growth arrest through the p53 pathway underscores the crucial regulatory role of ARID3A, ARID3B, and their interaction with lncRNAs MALAT1 and NORAD. In this study, we aimed to investigate the potential interactive and functional connections among ARID3A, ARID3B, MALAT1, and NORAD in NSCLC, considering their involvement in the pRB-E2F and p53 pathways. Our findings strongly suggest that ARID3A and ARID3B play a regulatory role in controlling MALAT1 and NORAD in NSCLC. Specifically, our study demonstrates that the activities of MALAT1 and NORAD were markedly increased upon the overexpression of ARID3A and ARID3B. Therefore, we can conclude that ARID3A and ARID3B likely contribute significantly to the oncogenic functions of MALAT1 and NORAD in NSCLC. Consequently, targeting ARID3A and ARID3B could hold promise as a therapeutic approach in NSCLC, given their direct control over the expression of MALAT1 and NORAD.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo
3.
Pathol Int ; 73(10): 490-496, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37589439

RESUMO

Psoriasis is an immune cell-dependent chronic autoimmune skin disorder. Interleukin 37 (IL-37) is a cytokine belonging to the IL-1 family that shows anti-inflammatory and protective effects in various mouse models of psoriasis. Even though various animal models are used to investigate the pathogenic mechanisms of psoriasis, human clinical studies are still needed to make up for the deficiencies, as animal models generally do not exhibit the complex phenotypic features of human psoriasis. Our study aims to demonstrate the relationship between IL-37-producing tissue-resident immune cells with the pathogenesis of psoriasis. The present study was performed on 28 psoriasis patients and 17 healthy volunteers. The ability of anti-inflammatory cytokine IL-37 to impede inflammation and regulate metabolic pathways was assessed by real-time quantitative polymerase chain reaction. Finally, immunofluorescence double staining for CD4+ IL-37b+ , CD68+ IL-37b+ , and (forkhead box protein P3) Foxp3+ IL-37b+ was performed. The proportion of CD4+ IL-37b+ T cells, CD68+ IL-37b+ macrophages, and Foxp3+ IL-37b+ T regulatory (Treg) cells was significantly increased in the psoriasis group compared to the control group. IL-37 gene expression was downregulated in psoriasis when contrasted to the control group. Our findings disclosed that IL-37-producing tissue-resident immune cells might be involved in the pathogenesis of psoriasis, and thus may be a therapeutic target for individuals with psoriasis.

4.
Biochem Biophys Res Commun ; 677: 81-87, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37556954

RESUMO

The objective of this study was to assess the impact of Vitamin E (Vit E) and Vitamin C (Vit C) on markers of the oxidant-antioxidant system, ovarian follicle reserves, and the surface epithelium in autologous intraperitoneal ovarian transplantation conducted in rats. The study aimed to investigate how these antioxidants influence various aspects related to transplantation outcomes, including oxidative stress markers, the preservation of follicle reserves, and the condition of the surface epithelium. A total of 20 adult female Wistar Albino rats were included in the study and randomly assigned to four different groups. Group 1, consisting of 5 rats, served as the control group and underwent a surgical procedure where their abdomens were opened and closed without any further intervention. Group 2, also consisting of 5 rats, underwent ovarian transplantation. In Group 3, comprising 5 rats, an intraperitoneal (IP) administration of 20 mg/kg body weight (b.w.) of Vitamin E (Vit E) was given 15 min prior to ovarian transplantation. Lastly, in Group 4, which included 5 rats, an IP administration of 50 mg/kg body weight (b.w.) of Vitamin C (Vit C) was given 15 min before ovarian transplantation. Vaginal cytology was performed in order to monitor the estrus phase in the rats. Biochemically, tissue and serum malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) levels were measured. Histopathologically, the number of dysplastic changes in the ovarian surface epithelium and primordial, primary, secondary, Graaffian, and atretic follicles were examined. Dysplastic changes in the surface epithelium of Group 2 were found to be significantly higher than in Group 1 and 4 (p < 0.02). In Group 2, the ovarian follicle reserves (primordial, primary, secondary, and Graaffian follicles) were significantly lower than in other groups (p < 0.02). In addition, a significant decrease in SOD levels was found in Group 2 compared to other groups (p < 0.02). The study showed that Vit E and Vit C in autologous intraperitoneal ovarian transplantation preserved the ovarian follicle reserve. Vit C was found to be more effective than Vit E.


Assuntos
Antioxidantes , Vitamina E , Ratos , Feminino , Animais , Vitamina E/farmacologia , Ratos Wistar , Antioxidantes/farmacologia , Folículo Ovariano/metabolismo , Ácido Ascórbico/farmacologia , Vitaminas/farmacologia , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Epitélio/metabolismo , Peso Corporal
5.
Biochem Biophys Res Commun ; 636(Pt 2): 97-103, 2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36368160

RESUMO

To examine the effects of 50 mg/kg and 150 mg/kg of propolis on ovarian folliculogenesis, p53 expression, and serum luteinising hormone (LH) and progesterone (P) levels in polycystic ovary syndrome (PCOS) modeled rats. Twenty-four Wistar female rats were divided into 4 experimental groups: Group 1 (G1, Control), Group 2 (G2, PCOS), Group 3 (G3, PCOS + 50 mg/kg propolis), and Group 4 (G4, PCOS + 150 mg/kg propolis). The PCOS model was induced via the administration of letrozole for 21 days. After 21 days, G3 and G4 received propolis (50 mg/kg or 150 mg/kg) by oral gavage for 10 days. Daily oestrous cycles were assessed to monitor PCOS formation. Histological examinations were carried out using haematoxylin and eosin (H&E) and Masson Trichrome (MT) staining. Ovarian follicles and corpus luteum (CL) structures were investigated. P and LH serum levels were determined by ELISA. A significant increase was observed in the number of cystic follicles in G2 compared to G1 (p < 0.001). Treatment with 50 mg/kg of propolis significantly ameliorated the elevated number of cystic and primary follicles seen in G2 (p < 0.001). Furthermore, G2 demonstrated a significant decrease in the number of CL structures (p < 0.05). Serum LH levels were significantly higher in G4 compared to both G1 and G2 (p < 0.01). No significant change was observed in circulating P levels. No p53 immunoreactivity was observed in any group. Low concentrations of propolis cannot completely improve the hormone profile and p53 expression associated with PCOS; however, these concentrations can control ovarian follicular cell architecture.


Assuntos
Síndrome do Ovário Policístico , Própole , Humanos , Feminino , Ratos , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Própole/farmacologia , Zona Pelúcida/metabolismo , Ratos Wistar , Hormônio Luteinizante
6.
Pathol Res Pract ; 235: 153951, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35644046

RESUMO

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.


Assuntos
Endometriose , Metformina , Animais , Apoptose , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Endometriose/patologia , Feminino , Humanos , Inflamação/tratamento farmacológico , Interleucina-6 , Interleucina-8 , Antígeno Ki-67 , Letrozol , Metformina/farmacologia , Metformina/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2
7.
Biochem Biophys Res Commun ; 606: 49-54, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35339751

RESUMO

This study was aimed at investigating the effects of melatonin, oxytetracycline and N-acetylcysteine on the ovarian follicle reserves and surface epithelium in autologous intraperitoneal ovarian transplantation in rats. Thirty adult female Wistar Albino were selected and randomly divided into six groups (n = 5). Group 1, which was the control group, only had their abdomens opened and closed while Group 2 underwent ovarian transplantation. Group 3, 4, 5 and 6 received 20 µg/kg/IM melatonin, 10 mg/kg/IM oxytetracycline, 150 mg/kg/IP N-Asetil sistein (NAC) and 1% ethanol respectively 15 min before the ovarian transplantation. Vaginal cytology was performed to monitor the estrus phase and the follicle reserve and changes in the surface epithelium were histopathologically evaluated during the preparations. Moreover, cellular apoptosis in tissues was evaluated with immunofluorescence staining of Bcl-2 and Bax. The Bax/Bcl-2 ratio was then calculated as the mean fluorescence intensity (MFI) of Bax and Bcl-2 MFI. Dysplastic change was found only significantly higher in the transplantation group (G2) (p < 0.01). Histopathologically, it was found that the follicle reserve was preserved significantly in the oxytetracycline and melatonin treated group (G3, G4) (p < 0.01). It was also observed that the oxytetracycline treated group (G4) were able to show better preventive effects against dysplastic changes of the surface epithelium. Moreover, the melatonin treated group depicted a low Bax/Bcl-2 ratio compared to the group that only underwent transplantation (G2) (p < 0.01). This study indicated that oxytetracycline and melatonin might be more effective than N-acetylcysteine in protecting against oxidative stress during ovarian transplantation.


Assuntos
Acetilcisteína , Melatonina , Ovário , Oxitetraciclina , Acetilcisteína/farmacologia , Animais , Feminino , Melatonina/farmacologia , Ovário/transplante , Oxitetraciclina/farmacologia , Ratos , Ratos Wistar , Proteína X Associada a bcl-2
8.
Reprod Biol ; 21(3): 100530, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34171715

RESUMO

Azoospermia is defined as the complete absence of sperm cells in the ejaculate. Approximately 10-15 % of infertile men display azoospermia. Azoospermia can be subdivided into two types, obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). NOA azoospermia might be the result due to primary testicular damage, secondary testicular damage, or incomplete testicular development. NOA azoospermia accounts for a considerable proportion of male infertility. A significant percentage of men with NOA azoospermia have foci of active spermatogenesis up to the stage of round spermatid. Round spermatid injection (ROSI) is a technique of assisted in-vitro fertilization (IVF) in assisted reproductive technology (ART). ROSI technique involves the injection of haploid germ cells derived from testicular biopsies into the recipient oocytes. The present study demonstrates that more participants and long-term follow-up studies are required to assess the reliability of the ROSI technique. In order to increase the success rate of the ROSI technique, round spermatids should be correctly evaluated and selected. Our study refers to the clinical values, challenges, and innovations in round spermatid injection (ROSI).


Assuntos
Injeções de Esperma Intracitoplásmicas/métodos , Espermátides , Azoospermia , Humanos , Masculino
9.
Gene ; 688: 140-150, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30529510

RESUMO

Moringa oleifera (Moringaceae) is a plant known for having high antioxidant potency, anticancer, hepatoprotective, cardioprotective etc. and many more activities. Besides these, Moringaceae has the potential for attenuating the male sexual dysfunction. Reactive oxygen species/ROS were increased in cryptorchidism and therefore cause infertility by damaging sperm DNA and germ cell apoptosis. There was an increase in heat shock proteins (HSP) in cells, which is affected by heat shock. In the present study, the antioxidant effects of two different doses of M. oleifera Lam Extract (MOLE) on experimentally induced cryptorchid testes of rats was investigated. Forty two male rats (16 days old) were divided into four groups: a normal control group, a cryptorchidism-induced control group and two cryptorchidism-induced groups treated orally with either 400 or 800 mg/kg MOLE for 2 weeks. Our study showed that there were ruptures from interstitial spaces, separation of the germ cells from basal membrane, falling of the germ cells into the lumen, perivascular fibrosis, oedema, increased level of HSP70, apoptosis, malondialdehyde (MDA) and decrease in the level of superoxide dismutase (SOD) after the cryptorchidism. We found that pathological damages, oxidative stress, expression of the HSP70 and germ cell apoptosis were decreased in treated groups with MOLE. In brief, we can say that aqueous extract of M. oleifera reduces the oxidative stress in a unilateral cryptorchidism induced rats, and it might attenuate histopathological damages, HSP expression and germ cell apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Células Germinativas/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Moringa oleifera/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Criptorquidismo/metabolismo , Células Germinativas/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismo
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