Comprehensive Overview of Innovative Strategies in Preventing Renal Ischemia-reperfusion Injury: Insights from Bibliometric and In Silico Analyses.

BACKGROUND: Ischemia-Reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion. AIM: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI. METHODS: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-Like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI. RESULTS: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice. CONCLUSION: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.

A Bibliometric and In Silico-Based Analysis of Anti-Lung Cancer Compounds from Sea Cucumber.

Lung cancer is one of the most lethal malignancies in the world. However, current curative approaches for treating this type of cancer have some weaknesses. Therefore, scientists are attempting to discover new anti-lung cancer agents. Sea cucumber is a marine-derived source for discovering biologically active compounds with anti-lung cancer properties. To explore the anti-lung cancer properties of sea cucumber, we analyzed surveys using VOSviewer software and identified the most frequently used keywords. We then searched the Google Scholar database for compounds with anti-lung cancer properties within that keyword family. Finally, we used AutoDock 4 to identify the compounds with the highest affinity for apoptotic receptors in lung cancer cells. The results showed that triterpene glucosides were the most frequently identified compounds in studies examining the anti-cancer properties of sea cucumbers. Intercedenside C, Scabraside A, and Scabraside B were the three triterpene glycosides with the highest affinity for apoptotic receptors in lung cancer cells. To the best of our knowledge, this is the first time that anti-lung cancer properties of sea cucumber-derived compounds have been examined in in silico conditions. Ultimately, these three components displayed anti-lung cancer properties in in silico conditions and may be used for the manufacture of anti-lung cancer agents in the near future.

Mesenchymal stromal/stem cell-derived exosomes and genitourinary cancers: A mini review.

Mesenchymal stromal/stem cell- (MSC-) derived exosomes are gaining popularity for their involvement in tissue repair and repressing various tumors through extensive patterns. Nevertheless, the impact of extracellular vesicles produced by stem cells on tumor formation and progression is controversial and seems to depend on several factors. The utilization of MSCs' various capabilities in urogenital neoplasms is widely regarded as a potential future therapeutic as well. These genitourinary neoplasms include prostatic neoplasms, ovarian neoplasms, cervical neoplasms, endometrial neoplasms, bladder neoplasms, and renal cell neoplasms. The present study has concentrated on the most recent information on genitourinary neoplasms employing MSCs derived exosomes' many capabilities, such as delivering effective RNAs, extensive tissue compatibility, and specificity with tumor identification without inherent limitations of cell therapy.

Male subfertility effects of sub-chronic ethanol exposure during stress in a rat model.

BACKGROUND: Stressful conditions increase alcohol consumption in men. Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but the effect of alcohol in a stress condition on male fertility is still relatively poorly understood. This project was undertaken to evaluate the effect of sub-chronic alcohol in a stress condition on male fertility in a rat model. METHODS: Male Sprague-Dawley rats were randomly divided into a control group, a stress group that was exposed to restraint stress, an ethanol group that was injected with ethanol daily, and a stress + ethanol group that was injected with ethanol daily and was exposed to restraint stress, simultaneously. Furthermore, testis tissue was evaluated histomorphometrically and immunohistochemically for apoptosis using a TUNEL assay after 12 days. Epididymis sperm analysis was done. Blood cortisol and testosterone were measured and expression of hypothalamic kisspeptin (Kiss1), RFRP-3, and MC4R mRNA were evaluated. RESULTS: Ethanol exposure during restraint stress did not alter body weight. Ethanol exposure decreased the cellular diameter and area, and stress increased the cellular diameter and area, in comparison with the control group. In the stress group, in comparison with the other groups, the number of seminiferous tubules decreased and the numerical density of seminiferous tubules increased. In addition, ethanol exposure and/or stress reduced semen analysis parameters (sperm viability and motility), but did not change serum testosterone concentrations. Apoptosis increased in spermatogonia with ethanol exposure, but spermatocytes were not affected. Our data present the novel finding that ethanol and stress reduced hypothalamic Kiss1 mRNA expression, while ethanol exposure decreased hypothalamic RFRP-3 and MC4R mRNA expression. CONCLUSIONS: Ethanol decreased cortisol hormone level during the restraint stress condition and attenuated hypothalamic reproductive-related gene expressions. Therefore, ethanol exposure may induce reduction of sperm viability, increased sperm mortality, and increased apoptosis, with long-term effects, and may induce permanent male subfertility.

Preventive Effects of Intrauterine Injection of Bone Marrow-Derived Mesenchymal Stromal Cell-Conditioned Media on Uterine Fibrosis Immediately after Endometrial Curettage in Rabbit.

Uterine fibrosis is an acquired disorder leading to menstrual irregularities, implantation impairment, and abortion. Mesenchymal stromal cells (MSCs) have antifibrotic properties through chemokine secretion. MSC-conditioned media (MSC-CM) contain paracrine components-exosomes-with a great potential for repairing damaged tissue or preventing fibrosis. The main goal of this study was to evaluate the preventive effects of bone marrow-derived MSC-CM (BM-MSC-CM) on uterine fibrosis after uterine curettage in rabbits. This study included 12 female rabbits (24 uterine horns in total). Excised uteri of each of the 12 female rabbits were randomly divided into four groups of intact negative control, curettage positive control, BM-MSC injection, and BM-MSC-CM injection in the way that two corresponding uteri from a rabbit were allocated to different groups. The MSC-CM were collected from cultivated BM-MSCs 48 hours after having been washed three times and replaced in serum-free media. Through a surgical approach, the caudal parts of the uteri were submitted to traumatic endometrial curettage, except for the intact negative uteri. After suturing the uterine walls, BM-MSCs or BM-MSC-CM were injected in the curettage site. Endometrial regeneration was histologically evaluated 30 days after treatment. Based on the evaluation of histomorphometric indices, curettage with or without preventive injections increased the growth of endometrial layers. However, the amount of fibrotic tissue in the CM and the BM-MSC injection groups was the same as the normal control groups, and all were less than the curettage group. A single injection of CM of MSCs after 30 days prevented the fibrotic tissue formation induced by curettage in endometrial layers of rabbits. Injecting BM-MSC-CM immediately after curettage prevented and reduced the uterine fibrosis similar to BM-MSCs in a rabbit model.

Benign prostatic hyperplasia treatment using plasmonic nanoparticles irradiated by laser in a rat model.

OBJECTIVE: In the current study we have stimulated the efficacy of plasmonic nanoparticles (NPs) by laser hyperthermia to achieve a less invasive method for tumor photothermal therapy of benign prostatic hyperplasia (BPH). METHODS: The levels of apoptosis on induced BPH in rats were assessed after treatment and revealed and recorded by various assayed. Moreover, the expression of caspases was considered to demonstrate the apoptotic pathways due to laser induced plasmonic NPs. RESULTS: In the Laser + NPs group prostate size of induced BPH decreased. Laser + NPs also decreased prostate specific antigen in comparison with the BPH groups. Furthermore, Laser + NPs attenuated BPH histopathologic indices in the rats. Laser + NPs induced apoptosis in prostatic epithelial cells via caspase-1 pathway. CONCLUSIONS: Altogether, the approach and findings from this study can be applied to introduce the laser irritated NPs method as a novel and less invasive therapy for patients suffering from BPH.

A combination of spearmint and flaxseed extract improved endocrine and histomorphology of ovary in experimental PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex reproduction and endocrine disorder of women in the reproductive age. Spearmint (Mentha spicata L.) has anti-androgenic activity and flaxseed (Linum usitatissimum L.) contains phytoestrogen and was reported to improve PCOS conditions. This study aimed to evaluate PCOS conditions following administration of a mixture of these two plants. METHODS: Twenty-four rats with regular cycles were randomly divided into four groups as control (C) and treatment-control (TC) received a combination of spearmint extract (SE) + flaxseed extract (FE). PCOS was induced in PCOS and treatment (T) groups by a single intramuscular injection of estradiol valerate. The treatment group received a combination of SE and FE for 30 days, 7 weeks after injection of estradiol valerate. Estrous cycles were monitored for 10 days and in the last day animals were sacrificed, ovaries were collected for the histomorphometric study and the serum levels of progesterone, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were measured. RESULT: Significant rise in progesterone and a decrease in testosterone and estradiol with no significant change of DHEA in the T group, was observed in comparison with the PCOS group (P < 0.05). No significant difference noticed between T and control groups (C &CT) regarding evaluated hormones. A significant increase in primary, pre-antral and antral follicles noticed in the T group compared to the PCOS group. The number of cystic follicles decreased in the T group compared with the PCOS group. Granulosa layer thickness increased while the thickness of theca decreased significantly in the T group compared to the PCOS group (P < 0.05). No significant endocrine or histological differences noticed between C and TC groups. CONCLUSION: A combination of flaxseed and spearmint extract improved the endocrine profile and the histomorphometric features of the ovary in the T group compared to the PCOS group.

Spermatogenesis after transplantation of adipose tissue-derived mesenchymal stem cells in busulfan-induced azoospermic hamster.

OBJECTIVES: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) with more potent immunomodulatory effects, greater proliferative potential and secretion of growth factors and cytokines in comparison with bone marrow derived MSCs are more appropriate for cell therapy. The aims of the present study were to evaluate the histomorphometric effect of AT-MSCs allotransplantation on regeneration of germinal layer cells of seminiferous tubules in busulfan-induced azoospermic hamsters. MATERIALS AND METHODS: In the present experimental case-control study, AT-MSCs were isolated from adipose tissue of two female and six male donor albino hamsters, and testes of the males were simultaneously used as negative control group. Six mature male recipient hamsters received two doses of busulfan with three weeks interval to stop endogenous spermatogenesis. Right testis of hamsters was intratubular injected with AT-MSCs via efferent duct 35 days after induction of azoospermia and was used as cell therapy group. The left testis without cell therapy was served as azoospermia group. RESULTS: After 35 days, testes and epididymis in all groups were removed for histological evaluation. Histomorphometric analyses of AT-MSCs-treated testes and epididymis showed that the epithelial tissue of seminiferous tubules was normally repaired in most cell-treated seminiferous tubules, and spermatozoa were present in epididymis tubes in comparison with intact testes. The untreated seminiferous tubules and epididymis tubes of azoospermia group were empty. CONCLUSION: Allotransplanted AT-MSCs could successfully induce spermatogenesis in azoospermic seminiferous tubules of hamster. Therefore, AT-MSCs can be suggested as an attractive candidate in cell transplantation of azoospermia.

Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat model.

OBJECTIVES: Herbal medicines are an alternative choice for treatment or controlling of polycystic ovary syndrome (PCOS). Effect of hydroalcoholic extract of flaxseed was evaluated on ovarian hormones and histological changes of uterus and ovary in a PCOS-induced rat model. MATERIALS AND METHODS: Twenty four rats divided into four groups including negative control, positive control, PCOS and treatment groups. Positive control group received hydroalcoholic extract of flaxseed for 30 days. PCOS was induced by single intramuscular injection of estradiol valerate. Treatment group was treated with flaxseed extract 7 weeks after induction of PCOS for 30 days. Ovaries and uterus were dissected out and their sections were used for histomorphometric study. Levels of estradiol, progesterone, testosterone and dehydroepiandrosterone (DHEA) were measured in the serum. RESULTS: In the treatment group, flaxseed extract increased level of progesterone (P<0.05), while decreased testosterone (P<0.05) compared with the PCOS group. Concentrations of estrogen and DHEA did not change significantly in comparison with the PCOS group. Histomorphometric study showed that in the treatment group, the number of preantral follicles, antral follicles and corpus luteum increased compared with the PCOS group (P<0.05), but the number of cystic follicles and diameter of antral follicles decreased (P<0.05), and the number of primary follicle did not alter significantly. In the treatment group, the thickness of granulosa layer increased, but the thickness of theca layer and tunica albuginea decreased compared to the PCOS group (P<0.05). CONCLUSION: Hormonal profile and histomorphometric features of ovary that were disturbed by PCOS induction were ameliorated by hydroalcoholic extract of flaxseed.

Spermatogenesis after Transplantation of Adipose Tissue-Derived Stem Cells in Azoospermic Guinea Pigs: A Histological and Histomorphometric Study.

BACKGROUND: The purpose of this research was to determine histomorphometric changes in busulfan-induced azoospermia after transplantation of Adipose Tissue-Derived Stem Cells (AdSCs) in guinea pig. AdSCs were isolated from adipose tissue around the testes of guinea pigs and characterized for mesenchymal properties. MATERIALS AND METHODS: Guinea pigs were allocated into three groups, including the control group without any intervention. To induce azoospermia, groups 2 and 3 received a dose of 40 mg/kg of busulfan with 21 days interval. Group 3 received 1×106 AdSCs in their seminiferous tubules of left testes, 35 days following last busulfan injection, while right testis in the group was considered for comparison as controls. Sixty days following transplantation of cell, histomorphometric and histopathologic changes of the experiments were assessed. RESULTS: After AdSCs' transplantation, normal spermatogenesis appearance was noticed compared to busulfan-induced azoospermia and AdSCs recovered spermatogenesis, and our findings can be added to the literature in treating azoospermic infertilities. CONCLUSION: The transplanted AdSCs could induce production of germinal cells using testicular seminiferous tubules and were an effective source in treating azoospermia.

Effects of hydroalcoholic extract of Ziziphus jujuba on acetic acid induced ulcerative colitis in male rat (Rattus norvegicus) / Efeitos do extrato hidroalcoólico de Ziziphus jujuba na colite ulcerativa induzida pelo ácido acético em rato macho (Rattus norvegicus)

Objective: To investigate the effects of hydroalcoholic extract of Ziziphus jujuba on the histopathological, tissue oxidative stress and inflammation plus to antioxidant pathways of colon tissue in rat with induced Ulcerative colitis. Materials and methods: Ulcerative colitis was induced in 80 rats those divided into 8 equal groups. Group 1 and 2 were negative controls receiving 1 mL/day of normal saline in enema and oral; group 3 and 4 as positive control 1 and 2 received 10 mg/kg of intra-colonic asacol and oral mesalazine; groups 5 and 6 received 20% and 40% of hydroalcoholic extract of Z. jujuba trans-rectally; group 7 and 8 received 1500 and 3000 mg/kg of hydroalcoholic extract of Z. jujuba orally, respectively. After 7 days, animals were evaluated for colon tissue histopathology, levels of malondialdehyde and IL-1ß, and activities of superoxide dismutase, glutathione peroxidase and myeloperoxidase in colon tissue. Results: Hydroalcoholic extract of Z. jujuba in both forms of trans-rectal and oral administration especially in the higher doses could result into a more healing effect in damaged colonic tissue, more reduce glutathione peroxidase and IL-1ß; level. Also, these two doses (gel 40% and oral 3000 mg/kg) could more decrease the myeloperoxidase activity and stimulate superoxide dismutase and glutathione peroxidase activities. Also, gel 40% in transrectal administration was more potent than administration 3000 mg/kg in oral. Conclusion: The results of the present study indicated that Z. jujube may be considered as a treatment of choice for Ulcerative colitis especially in gel form and also in dose-dependent pattern.

Objetivo: Investigar os efeitos do extrato hidroalcoólico de Ziziphus jujuba no estresse oxidativo em tecido ao nível histopatológico e na inflamação, juntamente com as vias antioxidantes em tecido de cólon em ratos com colite ulcerativa induzida. Materiais e métodos: Induzimos colite ulcerativa em 80 ratos, divididos em 8 grupos iguais. Os grupos 1 e 2 eram controles negativos que receberam 1 mL/dia de salina normal em enema e por via oral; os grupos 3 e 4 eram controles positivos para 1 e 2 e receberam 10 mg/kg de asacol por via intracolônica e mesalazina oral; os grupos 5 e 6 receberam gel a 20% e 40% de extrato hidroalcoólico de Z. jujuba por via trans-retal; os grupos 7 e 8 receberam 1500 e 3000 mg/kg de extrato hidroalcoólico de Z. jujuba por via oral, respectivamente. Transcorridos 7 dias, os animais foram avaliados para histopatologia de tecido de cólon, níveis de malonildialdeído e IL-1ß, e atividades de superóxido dismutase, glutátion peroxidase e mieloperoxidase no tecido colônico. Resultados: O uso do extrato hidroalcoólico de Z. jujuba, tanto na forma transretal como oral, e em especial nas doses mais altas, resultou em um efeito de cicatrização mais intensa no tecido colônico lesionado, e em maior redução nos níveis de glutátion peroxidase IL-1ß. Além disso, essas duas doses (gel a 40% e 3000 mg/kg por via oral) diminuíram ainda mais a atividade de mieloperoxidase e estimularam as atividades de superóxido dismutase e glutátion peroxidase. Outro achado do estudo foi que o gel a 40% por administração trans-retal se mostrou mais potente do que a administração oral de 3000 mg/kg. Conclusão: Os resultados do presente estudo sugerem que Z. jujuba pode ser considerado como tratamento de escolha para colite ulcerativa, sobretudo em forma de gel e também em um padrão proporcional à dose administrada.

Histomorphometric evaluation of treatment of rat azoosper-mic seminiferous tubules by allotransplantation of bone marrow-derived mesenchymal stem cells.

OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BM-MSCs) potentials make them appropriate for cell therapy including ability of differentiation and release of anti-inflammatory cytokines and growth factors secreta. For treatment of azoospermia to induce proliferation and differentiation of germ cells, MSCs transplantation has been introduced. The aim of the present experimental case-control study was to histomorphometric evaluation of the germinal cells in seminiferous tubules of azoospermic rats before and after BM-MSCs allotransplantation. MATERIALS AND METHODS: In the present study, BM-MSCs were isolated from six male rats and confirmed. Their testes also served as intact negative controls. The recipient rats (n=6) were received two doses of 10 mg/kg of busulfan with 21 days interval to induce azoospermia. After cessation of spermatogenesis, the rats were allotransplanted with the BM-MSCs into efferent duct of right testes. Thirty-five days later, the right cell-treated testes were compared to left azoospermic ones. RESULTS: Histomorphometric analyses showed that the seminiferous tubules treated with BM-MSCs had normal morphology in comparison with azoospermic testes, which were without germinal layer. In most BM-MSCs-treated seminiferous tubules, spermatogenesis was observed. CONCLUSION: The allotransplanted BM-MSCs could induce spermatogenesis in seminiferous tubules of azoospermic rats.

Induction of Asherman's Syndrome in Rabbit.

BACKGROUND: Uterine synechiae or Asherman's syndrome is a condition that can cause infertility. The present experimental study was designed to establish the rabbit as an animal model for human Asherman's syndrome using the endometrial curettage. METHODS: In an experimental study, female adult rabbits (n=18) were randomly divided into intact and ovariectomized groups. One third of caudal part of both uteri was submitted to traumatic endometrial curettage. One group was simultaneously ovariectomized. The intact rabbits were artificially induced ovulation during 10 days after surgery. One third of cranial part of both uteri was selected as the control. Synechiae occurring, luminal area/total area (LA/TA), endometrial area/total area (EA/TA), myometrial and perimetrial area/total area (MPA/TA), endometrial area/uterine wall area (EA/UWA), and myometrial and perimetrial area/uterine wall area (MPA/UWA) ratios of both uteri in six subdivided groups (n=6) were analysed in curetted and intact control parts. On days 15, 30 and 45 following surgery by two-way ANOVA and LSD test (p<0.05). RESULTS: Histopathologic findings showed significant epithelial damage together with significant inflammatory reaction in the intact curettage group. The LA/TA ratios of the intact curettage group on days 15 and 45 were more than the intact control group on day 15. The EA/TA ratio of the intact curettage group on day 30 was less than the intact control group on day 30. CONCLUSION: Uterine fibrosis was observed in intact curettage group, and this modified animal model showed a pathogenesis condition similar to intrauterine adhesions observed in human.

Induction of Spermatogenesis by Bone Marrow-derived Mesenchymal Stem Cells in Busulfan-induced Azoospermia in Hamster.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have potential of differentiation and they secrete anti-inflammatory cytokines and growth factors which make them appropriate for cell therapy. AIM OF THE WORK: Were to evaluate the healing effect of BM-MSCs transplantation on germinal cells of busulfan-induced azoospermic hamsters. MATERIAL AND METHODS: In the present experimental case control study, BM-MSCs were isolated from bone marrow of donor albino hamsters. Five mature male recipient hamsters received two doses of 10 mg/kg of busulfan with 21 days interval to stop endogenous spermatogenesis. After induction of azoospermia, right testis of hamsters was injected with 10(6) BM-MSCs via efferent duct and the left one remained as azoospermia control testis. Five normal mature hamsters were selected as normal intact control. After 35 days, testes and epididymis of three groups were removed for histological evaluation. RESULTS: Histomorphological analyses of BM-MSCs treated testes and epididymis showed the epithelial tissue of seminiferous tubules had normal morphology and spermatozoa were present in epididymis tubes. Spermatogenesis was observed in most cell-treated seminiferous tubules. The untreated seminiferous tubules were empty. CONCLUSION: Transplanted BM-MSCs could successfully induce spermatogenesis in seminiferous tubules of azoospermic hamster. Therefore, BM-MSCs can be an attractive candidate in cell transplantation of azoospermia.

Adipose tissue-derived mesenchymal stem cells repair germinal cells of seminiferous tubules of busulfan-induced azoospermic rats.

CONTEXT: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are less invasive than bone marrow mesenchymal stem cells to obtain for cell therapy. AIMS: The aims of this study were to evaluate the germinal cells characteristics and repairs in seminiferous tubules of busulfan-induced azoospermic rats after AT-MSCs transplantation. SETTINGS AND DESIGN: Experimental case-control study. MATERIALS AND METHODS: In the present experimental study, donors AT-MSCs were isolated from subcutaneous adipose tissue of two Sprague-Dawley rats. The recipients (n = 5) were received two doses of 10 mg/kg of busulfan with 21 days interval to stop endogenous spermatogenesis. After induction of azoospermia by busulfan, rats were injected with the AT-MSCs into the efferent duct of right testes. After 60 days, the right testes were injected AT-MSCs were compared to left azoospermic testes. Five untreated male rats served as negative control. STATISTICAL ANALYSIS USED: Stereological indices were analyzed by one-way ANOVA and LSD post-hoc test. The spermatogenesis index was compared using Mann-Whitney U test. RESULTS: After stereological analyses, the seminiferous tubules treated with AT-MSCs had normal morphology. The untreated seminiferous tubules were empty. Spermatogenesis was observed in most cell-treated seminiferous tubules. CONCLUSIONS: The testis of busulfan-induced azoospermic rats accepted transplanted AT-MSCs. The transplanted AT-MSCs could induce spermatogenesis in seminiferous tubules of the rat.