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Acaricidal and ovicidal activities of Clerodendrum viscosum Ventenat (Verbenaceae), a common weed of India, were investigated on tea red spider mite, Oligonychus coffeae Nietner (Acarina: Tetranychidae). Different solvent extracts (water, methanol, acetone and petroleum ether) of C. viscosum at different concentrations (1, 2, 4 and 8%) were used. These solvent extracts exhibited mortality of O. coffeae in the range of 40-90% in water, 67-97% in petroleum ether, 50-80% in acetone and 43-87% in methanol extract. Depending on LC50 values, the relative toxicity was found to be significantly highest against petroleum ether extracts and lowest in water extracts. Acetone extract of C.viscosum recorded maximum ovicidal activity followed by petroleum ether, methanol and the less by water extracts. In the field trials, mite population were significantly lower (P < 0.05) on plots sprayed with different of C. viscosum extracts than the control and at par with chemical acaricide and neem biopesticide. No phytotoxic effect (score, 0-5% and grade 1) was observed in the field from tea bushes sprayed with different doses of extracts of C. viscosum. Made tea samples were taint free. Organoleptic test revealed leaf infusions and liquor strength as good, scoring 6.5-7.0 on a 10-point scale. Availability and distribution of this weed (C. viscosum) in and around tea growing areas of sub-Himalayan region, along with its processing for the feasibility of including C.visosum extracts in the current IPM programme are discussed. [ABSTRACT FROM AUTHOR]

Among various biotic stresses that tea plants face, mite attack, especially from the tea red spider mite (Oligonychus coffeae, Acarina: Tetranychidae), has been a major challenge in recent years. The difference in relative toxicity of different commonly used acaricides to O. coffeae was observed in plantations of the tea-growing region of North Bengal, India. This study indicated that the relative susceptibility values (50% lethal concentration; LC50) of O. coffeae to different acaricides varied with region. O. coffeae populations of West Terai and South Terai showed less susceptibility to all acaricides tested compared with those from the Eastern Dooars. Populations of the Central Dooars, Western Dooars, and North Terai showed intermediate levels of susceptibility to different acaricides against O. coffeae. Ethion had the lowest efficacy to the pest in all tea-growing regions in North Bengal. Effective field dosages of these acaricides were compared with LC95 values, and a significant decrease in the susceptibility of the test population to ethion and dicofal was observed. As yet, there was little change for the newly introduced acaricides like fenazaquin, fenpropathrin, and propargite, which were effective at doses lower than the recommended dose. [ABSTRACT FROM AUTHOR]

In the present study, the near complete mitochondrial genome (mitogenome) of Junonia iphita (Lepidoptera: Nymphalidae: Nymphalinae) was determined to be 14,892 bp. The gene order and orientation are identical to those in other butterfly species. The phylogenetic tree constructed from the whole mitogenomes using the 13 protein coding genes (PCGs) defines the genetic relatedness of the two J. iphita species collected from two different regions. All the Junonia species clustered together, and were further subdivided into clade one consisting of J. almana and J. orithya and clade two comprising of the two J. iphita which were collected from Indo and Indochinese subregions separated by river barrier. Comparison between the two J. iphita sequences revealed minor variations and Single Nucleotide Polymorphisms were identified at 51 sites amounting to 0.4% of the entire mitochondrial genome.

The tea mosquito bug, Helopeltis theivora (Waterhouse), is an important economic pest of tea in India. The development of resistance in H. theivora populations obtained from a conventional plantation as compared with a strain from an organic plantation was studied in the laboratory for five generations, and associated changes in life cycle traits were assessed. Selection using sublethal concentrations of deltamethrin resulted in a 5.19-fold increase in insecticide resistance ratio from the F1 to the F5 generation in the H. theivora population from the conventional plantation. By the F5 generation, nymphal duration and total developmental duration and adult longevity were higher and fecundity was lower in the deltamethrin-selected strain than in the non-selected strain from a conventional plantation and the susceptible strain from an organic plantation. These findings have practical implications for insecticide resistance management of this important sucking pest of tea.

The copper nanoparticles (CuNPs) have widely been used for human welfare in the various applications. Despite its uses for beneficial purposes, CuNPs has been known to cause toxicity in the various organ based on the size, dose and duration. Both male and female reproductive functions have been to be compromised under CuNPs toxicity. The aim of this study is to investigate the effects of CuNPs after prolonged duration on the hypothalamus and pituitary in relation to the neuroendocrine regulation of reproduction in male mice since it has not been done before. Due to which the mice were orally treated with three doses of CuNPs viz. 10,100 and 200 mg/kg for 70 consecutive days to examines its adverse effects. The circulating GnRH levels and its abundance in the median eminence did not change in the CuNPs treated groups. However, circulating FSH showed significant decline in all the CuNPs treated groups, while LH was decline only in higher doses of CuNPs. The immunolocalization of LH and FSH also showed decreased abundance in the pituitary. Thus, pituitary function showed severely affected by CuNPs; the architecture of anterior pituitary also showed sign of degeneration such a presence of vacuoles and it was also shown that CuNPs treated groups have higher level of MDA which is an oxidative stress marker as indicated by the MDA staining. Moreover, the abundance of GnRHR and AR exhibited less abundance in the pituitary of higher dose of CuNPs treated groups. Thus, it can be concluded that pituitary becomes less responsive for hypothalamic GnRH and gonadal steroid, which could be reason of suppressed gonadotropin in the CuNPs treated mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Visfatin is expressed in the testis of chicken, humans and rodents; however, direct role of visfatin in the adult testis has not been studied. We investigated testicular responses after intra-testicular injection of FK866. The effects of visfatin inhibition were accessed at 24 hrs and 1 week post FK866 treatment. The testicular histoarchitecture were degenerated after 24 hrs of FK866 treatment along with supressed testosterone and proliferating markers and resumption in these parameters showed after 1 week. The expression of AR and ERα were down-regulated after 1 week of FK866 treatment. The expression of BCl2 was down-regulated along with a slight elevation of caspase3 after 24 hrs; however, both proteins still showed suppressed expression after 1 week. Furthermore, ERβ expression, 3βHSD, and 17βHSD were down-regulated in both groups compared to the control. Despite the down-regulation of some factors, the testicular proliferation and histoarchitecture showed resumption in the testis after 1 week of FK866 treatment. This could be due to increased testosterone secretion by suppressing aromatase expression. In conclusion, our result is the first report on the direct role of visfatin in the adult testis. Visfatin has a stimulatory role in testosterone synthesis and proliferation in the testis. Moreover, some deregulated factors in the testis after 1 week of FK866 treatment, despite normal histoarchitecture treatment, could be a compensatory mechanism after visfatin inhibitions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Antimicrobial peptides (AMPs) are gaining popularity as potential substitutes for conventional antibiotics and bio-preservatives in response to an increase in antimicrobial resistance cases. However, their poor pharmacokinetic profiles limit their applicability. This study using ADMETlab, OECD QSAR toolbox, and VEGA HUB virtual environments profiled 82 peptide sequences of seven bee antimicrobial peptides (BAMPs: abaecin, apamin, apisimin, apidaecin, defensin, hymenoptaecin, and melittin) using 81 descriptors combining physicochemical, medicinal chemistry, ADMET, and toxicophore criteria. BAMPs adhere to key drug-like physicochemical features and drug-ability regulations set forth by pharmaceutical giants, including Lipinski, Pfizer, and GlaxoSmithKline. BAMPs have been predicted to demonstrate favorable cell permeability, high water solubility, oral bioavailability, no blood-brain barrier penetration, oral and intestinal absorption, excretion, and a high therapeutic index. They function as non-substrates of p-glycoprotein and do not alter the pharmacokinetic effects of P-gp substrates. None of BAMPs were found to inhibit cytochrome P450 enzymes, indicating their potential to promote drug clearance and metabolism. BAMPs are safe from adverse reactions, free of respiratory toxicity, hERG blockers, hepatotoxicity, sensitizers, carcinogens, and mutagens. They are non-corrosive, non-irritating to the eyes, non-bioaccumulative, non-ecotoxic, antibacterial, antifungal, and antiviral, low toxic with no toxicophore or PAINS alerts recorded. They are non-toxic to various receptors, including gonadal and stress receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. Seven BAMPs have been tested for their drug-like properties, supporting their potential as potential leads for the pharmaceutical and food industries as antimicrobial agents and bio-preservatives. Future studies should optimize bee peptide expression in biological systems.

Hyperandrogenemia is associated with polycystic ovarian syndrome (PCOS) and imbalances in the pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Apelin and its receptor, APJ (class A, rhodopsin-like G- protein-coupled receptor), belongs to adipokines, and its expression has been shown in the pituitary. It is also well known that, hyperandrogenism and PCOS have deregulation of different adipokines. Whether hyperandrogenism also deregulates the apelin system in the pituitary has yet to be investigated. Thus, we have investigated the expression and localization of apelin and its receptor, APJ, in the letrozole-induced hyperandrogenised pituitary of female mice. Our results showed that the apelin, APJ and androgen receptor (AR) expression were upregulated in the anterior pituitary. Furthermore, the immunostaining of LH exhibited increased abundance than FSH. The circulating LH was also found to be elevated compared to FSH levels. The increased LH synthesis and secretion coincides with elevated apelin system in the pituitary of hyperandrogenised mice. Recently, a direct role of apelin has also been reported in the female pituitary, where apelin inhibits LH secretion. Thus, apelin could be one of the factors for deregulated gonadotropin secretion in hyperandrogenised conditions. However, more research is needed to fully understand the complex interactions between apelin and androgen regarding gonadotropin secretion in hyperandrogenised conditions., (© 2024 Wiley Periodicals LLC.)

Heat stress has been shown to have a detrimental impact on testicular activity and spermatogenesis. Ellagic acid is a plant-derived organic compound that has a variety of biological functions. Thus, it is believed that ellagic acid may improve heat-stressed testicular dysfunction. There has been no research on the impact of ellagic acid on heat-stressed testicular dysfunction. The mice were divided into 4 groups. The first group was the normal control group (CN), and the second received heat stress (HS) by submerging the lower body for 15 min in a water bath with a thermostatically controlled temperature kept at 43°C (HS), and the third and fourth groups were subjected to heat-stress similar to group two and given two different dosages of ellagic acid (5 mg/kg (EH5) and 50 mg/kg (EH50) for 14 days. Ellagic acid at a dose of 50 mg/kg improved the level of circulating testosterone (increased 3βHSD) and decreases the oxidative stress. The testicular and epididymal architecture along with sperm parameters also showed improvement. Ellagic acid treatment significantly increases the germ cell proliferation (GCNA, BrdU staining) and Bcl2 expression and decreases active caspase 3 expression. Heat stress downregulated the expression of AR, ER-α and ER-β, and treatment with ellagic acid increased the expression of ER-α and ER-β markers in the 50 mg/kg treatment group. Thus, our finding suggests that ellagic acid ameliorates heat-induced testicular impairment through modulating testosterone synthesis, germ cell proliferation, and oxidative stress. These effects could be manifested by regulating androgen and estrogen receptors. However, the two doses showed differential effects of some parameters, which require further investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of in this publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The present study investigated the possible effects of copper nanoparticles (CuNPs) after discontinuing treatment on testicular activity in a mouse model. The male mice were given continuous CuNPs treatment for 70 days and left untreated for 70 days. The results show that even after the discontinuation of CuNPs treatment, the testicular impairment was persistent till 140 days at a higher dose (200 mg/kg group). The spermatogenesis, sperm parameters, proliferation and antioxidant status were suppressed in the higher dose groups. However, these effects were also observed at moderate levels in the other CuNPs treated groups, such as at 10 mg/kg and 100 mg/kg. The apoptosis was stimulated at a higher dose compared to the other groups. The testosterone, LH levels and AR expression were suppressed in all the CuNPs treated groups, along with slight elevation in the estrogen levels and up-regulated ERβ expression. The fertility data also showed a decline in all CuNPs treated groups with the lowest litter size in the 200 mg/kg treated group. Despite testis, epididymis and accessory sex organs like prostate, seminal vesicle, and vas deferens, histoarchitecture also showed impairment. This is the first report on how CuNPs affect the male reproductive system in mice even after treatment was terminated. The current study also demonstrated possible negative effects on male reproductive function that might last for longer at higher dosages of chronic CuNPs exposure even after termination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Apelin and APJ have been shown to regulate female reproductive functions. However, its uterine expression during the oestrous cycle and its regulation by ovarian steroids, along with gonadotropin regulation in the ovary, has not been investigated. This study aimed to analyze the steroid-dependent uterine expression of apelin/APJ in the uterus along with the oestrous cycle. Furthermore, it also aimed to investigate gonadotropin-dependent ovarian expression of apelin and APJ. To investigate the uterine expression of apelin and APJ during estrous cycle in mice, uterus at different estrous stage were collected. To explore the ovarian steroids dependent expression of apelin system in the uterus, ovariectomized mice were treated with only estrogen at dose of 30 ng/g, only progesterone at dose of 150 μg/g and combined doses. To study the effect of gonadotropin on ovarian expression of apelin system, immature mice were injected with 2.5 IU of pregnant mare serum gonadotropin (PMSG) alone and both PMSG plus 2.5 IU of chorionic gonadotropin (hCG). Apelin and APJ protein expression are modulated by estrous phases in the uterus. The uterine apelin and APJ expression are up-regulated by estrogen and down-regulated by progesterone. The expression and localization of APJ showed increased abundance in the follicles of PMSG treated mice, however, the PMSG plus HCG treatment showed formation of corpus luteum with increased abundance of APJ and progesterone secretion. The expression of apelin and APJ are regulated by pituitary gonadotropin in the ovary and uterine apelin system by ovarian steroid hormone., Competing Interests: Declaration of Competing Interest All authors declared that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Aims: Polycystic ovarian syndrome (PCOS) is one of the most common (about 5-20%) reproductive disorders in women of reproductive age; it is characterized by polycystic ovaries, hyperandrogenism, and oligo/ anovulation. The levels and expression of ovarian adipokines are deregulated in the PCOS. Apelin is an adipokine that acts through its receptor (APJ) and is known to express in the various tissues including the ovary. It has also been suggested that apelin and APJ could be targeted as therapeutic adjuncts for the management of PCOS. However, no study has been conducted on the management of PCOS by targeting the apelin system. Thus, we aimed to evaluate its impact on combating PCOS-associated ovarian pathogenesis., Methods: The current work employed a letrozole-induced-hyperandrogenism PCOS-like mice model to investigate the effects of apelin13 and APJ, antagonist ML221. The PCOS model was induced by oral administration of letrozole (1 mg/kg) for 21 days. A total of four experimental groups were made, control, PCOS control, PCOS + aplein13, and PCOS + ML221. The treatment of apelin13 and ML221 was given from day 22 for two weeks., Key Findings: The letrozole-induced PCOS-like features such as hyperandrogenism, cystic follicle, decreased corpus luteum, elevated levels of LH/FSH ratio, and up-regulation of ovarian AR expression were ameliorated by apelin13 and ML221 treatment. However, the PCOS-augmented oxidative stress and apoptosis were suppressed by apelin 13 treatments only. ML221 treatment still showed elevated oxidative stress and stimulated apoptosis as reflected by decreased antioxidant enzymes and increased active caspase3 and Bax expression. The expression of ERs was elevated in all groups except control. Furthermore, the PCOS model showed elevated expression of APJ and apelin13 treatment down-regulated its own receptor. Overall, observing the ovarian histology, corpus luteum formation, and decreased androgen levels by both apelin13 and ML221 showed ameliorative effects on the cystic ovary., Significance: Despite the similar morphological observation of ovarian histology, apelin13 and ML221 exhibited opposite effects on oxidative stress and apoptosis. Therefore, apelin13 (which down-regulates APJ) and ML221 (an APJ antagonist) may have suppressed APJ signalling, which would account for our findings on the mitigation of polycystic ovarian syndrome. In conclusion, both apelin13 and ML221 mediated mitigation have different mechanisms, which need further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Di-(2-ethylhexyl) phthalic acid (DEHP) pollutes the environment, and posing a significant risk to human and animal health. Consequently, a successful preventative strategy against DEHP-induced liver toxicity needs to be investigated. Morin hydrate (MH), a flavanol compound, possesses toxic preventive attributes against various environmental pollutants. However, the effects of MH have not been investigated against DEHP-induced liver toxicity. Female Swiss albino mice were divided into four groups: control, DEHP (orally administered with 500 mg/kg, DEHP plus MH 10 mg/kg, and DEHP plus MH 100 mg/kg for 14 days. The results showed that the MH treatment ameliorated the DEHP-induced liver dysfunctions by decreasing the alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin, liver histoarchitecture, fibrosis, and markers of oxidative stress. Furthermore, DEHP increased apoptosis, increased active caspase 3 and decreased B cell lymphoma-2 (Bcl-2) expression. However, the MH treatment showed a differential effect on these proteins; a lower dose increased, and a higher dose decreased the expression. Thus, a lower dose of MH could be involved in the disposal of damaged hepatocytes. Expression of Estrogen receptors alpha (ERα) also showed a similar trend with active caspase 3. Furthermore, the expression of Tumor necrosis factor alpha (TNF-α) and Nuclear factor-κβ (NF-κβ) were up-regulated by DEHP treatment, and MH treatment down-regulated the expression of these two inflammatory markers. Since this down-regulation of TNF-α and NF-κβ coincides with improved liver functions against DEHP-induced toxicity, it can be concluded that MH-mediated liver function involves the singling of TNF-α and NF-κβ., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The adipokines, visfatin, chemerin, and its receptor are expressed in the testis. It has also been shown that heat-stress alters the secretion and expression of other adipokines. Testicular heat-stress is now well known to cause the impairment in the testis. It has also been documented that heat-stress changes the expression of genes and proteins in the testis. To the best of our knowledge, the expression and localization of visfatin chemerin and its receptor have not been investigated in the heat-stressed testis. Therefore, the present study has investigated the expression and localization of these proteins in the heat-stressed testis. The expression of visfatin and chemerin and receptor exhibits a differential repossess against the heat stress. Visfatin expression was up-regulated while chemerin and chemerin receptor was down-regulated in the heat-stressed testis as shown by western blot analysis. The immunolocalization of visfatin and chemerin showed increased abundance in the seminiferous tubules of heat-stressed mice testis. Furthermore, abundance of visfatin, chemerin, and its receptor showed a decrease in abundance in the Leydig cells of heat-stressed testis. The decreased abundance of these proteins in the Leydig cells coincides with decreased 3β-HSD immunostaining along with decreased testosterone levels. These results suggest that heat-stress might decrease testosterone secretion by modulating visfatin and chemerin in the Leydig cells. The increased abundance of visfatin and chemerin in the primary spermatocytes, round spermatid, and multinucleated germ cells also coincides with increased immunostaining of active caspase-3. Moreover, expression of Bcl-2 was down-regulated, and expression of active caspase-3 and HSP70 were up-regulated along with increased oxidative stress in the heat-stressed testis, suggesting stimulated apoptosis. In conclusion, our results showed that visfatin, chemerin, and its receptor are differentially expressed in the testis under heat-stress and within the testis also it might differentially regulate testosterone biosynthesis in the Leydig cells and apoptosis in the seminiferous tubules., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of in this publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: It is now well known that visfatin is expressed in the testis and ovary of various animals. Visfatin is known to regulate gonadal functions such as steroidogenesis, proliferation, and apoptosis in the ovary and testis of mice. Recently, we have shown that visfatin has an inhibitory role in the infantile mice testis. It has also been shown that visfatin stimulates testicular steroidogenesis in adult rats. However, the role of visfatin during puberty has not been investigated in relation to the above-mentioned process., Objective: The objective of the present study was to examine the effect of visfatin inhibition by FK866 from PND25 to PND35 (pre-pubertal to early pubertal) in male Swiss albino mice on steroidogenesis, proliferation, and apoptosis., Methods: Sixteen mice (25 days old) were divided into two groups, one group was given normal saline and the other group was administered with an inhibitor of visfatin (FK866) at the dose of 1.5 mg/kg by intraperitoneal injection for 10 days. Histopathological and immunohistochemical analysis, western blot analysis and hormonal assay were done., Results: Visfatin inhibition resulted in increased estrogen secretion, body weight, seminiferous tubule diameter, germinal epithelium height, and proliferation along with increased expression of BCl2, casapse3, ERs and aromatase expression in the mice testis. Visfatin inhibition down-regulated the testicular visfatin expression and also decreased abundance in the adipose tissues., Conclusion: In conclusion, decreased AR expression and increased ERs expression by FK866, suggest that visfatin might have a stimulatory effect on AR signaling than ERs in the early pubertal stage of mice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The apelin receptor (APJ) belongs to the member of the G protein-coupled receptor family, and expression of APJ has been reported in the different cell types of testis. The seminiferous tubules in the testis can be identified as different stages (I-XII). It has been also suggested that different factors could be expressed in stage and cell-specific manner in the seminiferous tubules. Recently, we also shown that expression of APJ is developmentally regulated in the testis from PND1 to PND42. Therefore, we analyzed the expression of APJ in the testis of adult mice by immunohistochemistry. Immunohistochemistry showed that the APJ was highly specific for the round and elongated spermatids with stage-dependent changes. The seminiferous tubules at stages I-VII showed APJ immunostaining in the spermatid steps 1-8, not steps of 13-16. The seminiferous tubules at stages IX-XII showed APJ immunostaining in the spermatid steps 9-12. These results suggested the possible role of APJ in the spermiogenesis process. The intratesticular administration of APJ antagonist, ML221 showed a few round spermatids in the seminiferous tubules and some of the tubules with complete absence of round spermatid. Overall, we present evidence that APJ expression in spermatid is dependent on the stages of the seminiferous epithelium cycle and APJ could be involved in the differentiation of round spermatid to elongated spermatid., (© 2024 Wiley Periodicals LLC.)

Apelin and its receptor (APJ) are expressed in the reproductive organs of some mammalian females. The function of oviduct has also been suggested to be compromised in the hyperandrogenism condition. However, expression of apelin and APJ has not been shown in the oviduct of hyperandrogenized mice. Thus, the present study has investigated the localization and expression of apelin and APJ in the letrozole-induced hyperandrogenized mice oviduct. Histomorphometric analysis showed decreased lumen of oviduct in the hyperandrogenized mice. Our results showed elevated expression of APJ and decreased abundance of apelin in the hyperandrogenized mice oviduct. This finding suggests impaired apelin signaling in the oviduct of hyperandrogenized mice. The expression of androgen receptor was upregulated while estrogen receptors were downregulated in the hyperandrogenized mice. The expression of HSP70 was also downregulated along with increased expression of active caspase 3 and BAX and decreased expression of BCL2 in hyperandrogenized mice. Furthermore, the phosphorylation of phospho-Ser473-Akt and phospho-Thr308-Akt also showed differential levels in the oviduct of hyperandrogenized mice. Whether this differential phosphorylation of Akt was solely due to impaired apelin signaling in the oviduct, remains unclear. Moreover, increased androgen signaling and suppressed estrogen signaling coincides with elevated apoptosis. In conclusion, hyperandrogenized conditions could also impair the gamete transport and fertilization process due to apoptosis in the oviduct. However, further study would be required to unravel the exact role of apelin signaling in the oviduct in relation to apoptosis., (© 2024 International Federation of Cell Biology.)

The expression of adipokines is well-known in the ovary and uterus. Recently we have shown that apelin and its receptor, APJ are developmentally regulated in the ovary and uterus of mice with elevation at postnatal day 14 (PND14). However, its role in the ovary and uterus of PND14 has not been investigated. Thus, we aimed to unravel the role of the apelin system (by APJ antagonist, ML221) on ovarian steroid secretion, proliferation, and apoptosis along with its role in uterine apoptosis in PND14 mice by in vitro approaches. The treatment of ML221 decreased estrogen, testosterone, and androstenedione secretion while increasing the progesterone secretion from the infantile ovary. These results suggest that apelin signaling would be important for ovarian estrogen synthesis in infantile mice (PND14). The abundance of 3β-HSD, 17β-HSD, aromatase, and active caspase3 increased in the infantile ovary after ML221 treatment. The expression of ERs and BCL2 were also down-regulated by ML221 treatment. The decreased BCL2 and increased active caspase3 by ML221 suggest the suppressive role of apelin on ovarian apoptosis. The APJ antagonist treatment also down-regulated the ER expression in the uterus along with increased active caspase3 and decreased BCL2 expression. In conclusion, apelin signaling inhibits the ovarian and uterine apoptosis via estrogen signaling in the ovary and uterus., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although the usage of nanoparticles has expanded substantially in recent years, and it causes the detrimental effect on the various organs. CuNPs are widely used in commercial applications. There has been minimal investigation into the possibly harmful effects of CuNPs on the accessory reproductive organs. Thus, the present study aimed to investigate the effect of CuNPs on the male reproductive organs like epididymis, vas deferens, seminal vesicle and prostate of mice. The mice were exposed orally to CuNPs at three doses 10, 100, and 200 mg/kg for 70 days. Our results showed that the organs index of only vas deferens and prostate reduced at 200 mg/kg group compared to the control. However, the histological study showed degenerative changes in the epididymis at higher doses like distortion in the tubules. The sperm parameters were also decreased in the 200 mg/kg CuNPs group. The vas deferens in 100 and 200 mg/kg treatment groups exhibited detachment of luminal epithelium and with a few or no spermatozoa in the higher dose group. The seminal vesicle and prostate also showed degenerative changes like atrophy, hyperplasia, and scant secretary materials. Furthermore, CuNPs also increased the oxidative stress and decreased antioxidant enzymes in vas deferens and seminal vesicles at higher dose. Caput epididymis showed decreased GPx enzymes in all the groups. However, MDA and GPx in corpus, cauda, and prostate did not show any significant variations among all the groups. In conclusion, our results suggest that CuNPs can manifest the detrimental effect of the male accessory organs and epididymis in a dose and tissue dependent manner. Since, detrimental effects were observed only at higher dose, thus, uses of CuNPs would be safe for reproductive organs at lower dose, even for the prolonged duration., (© 2023 Wiley Periodicals LLC.)

Background: Heat stress is known to adversely affect testicular activity and manifest the pathogenesis of spermatogenesis. Morin hydrate is a plant-derived compound, which contains a wide range of biological activities. Thus, it is hypothesized that morin hydrate might have an ameliorative effect on heat-induced testicular impairment. There has not been any research on the impact of morin hydrate on heat-induced testicular damage., Methods: The experimental mice were divided into four groups, groups1 as the normal control group (CN), and the second which underwent heat stress (HS) by immersing the lower body for 15 min in a thermostatically controlled water bath kept at 43 °C (HS), and third and fourth heat-stressed followed by two different dosages of morin hydrate 10 mg/kg (HSM10) and 100 mg/kg (HSM100) for 14 days., Results: Morin hydrate treatment at 10 mg/kg improved, circulating testosterone levels (increases 3βHSD), and oxidative stress along with improvement in the testis and caput and corpus epididymis histoarchitecture, however, both doses of morin hydrate improved sperm parameters. Morin hydrate treatment significantly increases germ cell proliferation, (GCNA, BrdU staining), expression of Bcl2 and decreases expression of active caspase 3. Heat stress also decreased the expression of AR, ER- α, and ER-β, and Morin hydrate treatment increased the expression of these markers in the 10 mg/kg treatment group., Conclusion: Morin hydrate ameliorates heat-induced testicular impairment modulating testosterone synthesis, germ cell proliferation, and oxidative stress. These effects could be manifested by regulating androgen and estrogen receptors. However, the two doses showed differential effects of some parameters, which requires further investigations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2, TMPRSS2, RBD/ACE2, RdRp, MPro, and PLPro) using ADMET, drug-likeness, molecular docking (AutoDock, FireDock and HDOCK), molecular dynamics simulation and MM-PBSA tools. One thousand Parkia bioactive entities were screened out by virtual screening and forty-five bioactive phytomolecules were selected based on favorable binding affinity and acceptable pharmacokinetic and pharmacodynamics properties. The binding affinity values of Parkia phyto-ligands (AutoDock: -6.00--10.40 kcal/mol; FireDock: -31.00--62.02 kcal/mol; and HDOCK: -150.0--294.93 kcal/mol) were observed to be higher than the reference antiviral drugs (AutoDock: -5.90--9.10 kcal/mol; FireDock: -35.64--59.35 kcal/mol; and HDOCK: -132.82--211.87 kcal/mol), suggesting a potent modulatory action of Parkia bioactive entities against the SARS-CoV-2. Didymin, rutin, epigallocatechin gallate, epicatechin-3-0-gallate, hyperin, ursolic acid, lupeol, stigmasta-5,24(28)-diene-3-ol, ellagic acid, apigenin, stigmasterol, and campesterol strongly bound with the multiple targets of the SARS-CoV-2 receptors, inhibiting viral entry, attachment, binding, replication, transcription, maturation, packaging and spread. Furthermore, ACE2, TMPRSS2, and MPro receptors possess significant molecular dynamic properties, including stability, compactness, flexibility and total binding energy. Residues GLU-589, and LEU-95 of ACE2, GLN-350, HIS-186, and ASP-257 of TMPRSS2, and GLU-14, MET-49, and GLN-189 of MPro receptors contributed to the formation of hydrogen bonds and binding interactions, playing vital roles in inhibiting the activity of the receptors. Promising results were achieved by developing multi-targeted antiviral Parkia bioactive entities as lead and prospective candidates under a small molecule strategy against SARS-CoV-2 pathogenesis. The antiviral activity of Parkia bioactive entities needs to be further validated by pre-clinical and clinical trials.

Introduction: Apelin is an endogenous peptide, whose expression has been shown in the hypothalamus, pituitary, and ovary; furthermore, it is also called a neuropeptide, binding to apelin receptor (APJ) for various functions. It has been suggested that the hypothalamus, pituitary, and ovarian (HPO) axis is tightly regulated and factors and functions of the HPO axis can be modulated during the estrous cycle to influence reproductive status. To the best of our knowledge, the status of apelin and its receptor, APJ has not been investigated in the HPO axis during the estrous cycle., Methods: To explore the expression of apelin and APJ in the HPO axis of mice during the estrous cycle, mice were divided into four groups: proestrus (Pro), estrus (Est), metestrus (Met), and diestrus (Di), and apelin and APJ were checked. Further, to explore the role of apelin in gonadotropin secretion, an in vitro study of the pituitary was performed at the Pro and Est stages., Result: The expression apelin and APJ in the hypothalamus showed elevation during the estrous cycle of postovulatory phases, Met, and Di. The immunolocalization of apelin and APJ in the anterior pituitary showed more abundance in the Est and Di. Our in vitro results showed that gonadotropin-releasing hormone agonist stimulated luteinizing hormone secretion was suppressed by the apelin 13 peptide from the pituitary of Pro and Est phases. This suggests an inhibitory role of apelin on gonadotropin secretion. The ovary also showed conspicuous changes in the presence of apelin and APJ during the estrous cycle. The expression of apelin and APJ coincides with folliculogenesis and corpus luteum formation and the expression of the apelin system in the different cell types of the ovary suggests its cell-specific role. Previous studies also showed that apelin has a stimulatory role in ovarian steroid secretion, proliferation, and corpus luteum., Conclusion: Overall our results showed that the apelin system changes along the HPO axis during the estrous cycle and might have an inhibitory at level of hypothalamus and pituitary and a stimulatory role at ovarian level., (© 2023 S. Karger AG, Basel.)

The expression of apelin and its receptor (APJ) has been shown in the hypothalamus-pituitary-testicular axis. It has also been suggested apelin and APJ are neuropeptide factors. The presence of apelin and APJ in the seminiferous tubules and interstitium might be predicted to act as a local regulator of testicular activity, although the function is not well known in the mice testis. In the present study, we have investigated the effects of APJ, antagonist, ML221 on the gonadotropin levels, testicular steroidogenesis, proliferation, apoptosis and antioxidant system. Our results showed that inhibition of APJ by ML221 increased the sperm concentration, circulating testosterone, FSH, LH levels and intra-testicular testosterone concentration. Furthermore, ML221 treatment stimulates the germ cell proliferation and antioxidant system in the testis. The expression of BCL2, AR was up-regulated whereas, the expression of BAX and active caspase3 was down-regulated after ML221 treatment. Immunohistocehmical analysis of AR also showed increase abundance in the spermatogonia, primary spermatocytes and Leydig cells of 150 μg/kg dose group. These findings suggest that in adult testis, the apelin system might have an inhibitory role in germ cell proliferation and a stimulatory role in apoptosis. It might also be suggested that the apelin system could be involved in the disposal mechanism for damaged germ cells during spermatogenesis via the down-regulation of AR., Competing Interests: Declaration of Competing Interest The authors verify that this work has not been published previously, is not under consideration for publication elsewhere, that it is approved by all authors, and that if accepted for publication, it will not be published elsewhere in the same form without written consent of the copyright-holder., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cadmium (Cd) is one of the heavy metal pollutants present in the environment due to human intervention. It is well known that Cd causes toxicological effects on various organs, including the testes. Morin hydrate is a plant-derived bioflavonoid with antioxidant, anti-inflammatory, and anti-stress properties. Thus, the question can be raised as to whether Morin has an effect on Cd-intoxication-induced testicular impairment. Therefore, the aim of this study was to investigate the role of Morin on Cd-mediated disruption of testicular activity. Mice were divided into three groups: group 1 served as the control group, group 2 was given Cd (10 mg/kg) orally for 35 days, and group 3 was given Cd and Morin hydrate (100 mg/kg) for 35 days. To validate the in vivo findings, an in vitro study on testicular explants was also performed. The results of the in vivo study showed that Cd-intoxicated mice had testicular disorganization, reduced circulating testosterone levels, decreased sperm density, and elevated oxidative stress and sperm abnormality. The expression of the germ cell proliferation marker, germ cell nuclear acidic protein (GCNA), and adipocytokine visfatin were also downregulated. It was observed that Morin hydrate upregulated testicular visfatin and GCNA expression in Cd-intoxicated mice, along with improvement in circulating testosterone, testicular histology, and sperm parameters. Furthermore, the in vitro study showed that Cd-mediated downregulation of testicular visfatin and GCNA expression, along with the suppressed secretion of testosterone from testicular explants, was normalized by Morin treatment, whereas visfatin expression was not. Overall, these data indicate that environmental cadmium exposure impairs testicular activity through downregulation of visfatin and GCNA expression, and Morin might play a protective role against Cd-induced testicular toxicity., (© 2023 Wiley Periodicals LLC.)

Copper nanoparticles (CuNPs) have been widely utilized in various applications. Due to its wider application, humans are at risk of its exposure. It has been reported that the exposure of CuNPs can lead to organ accumulation and affect organ toxicity. Recent study suggested that CuNPs can translocate into the uterus and affect uterine injury in rat, whereas uterine toxicity still remains unclear. The uterus is an important female organ which is required to sustain pregnancy. Thus, uterine structure and physiology are important. Therefore, this study hypothesized that CuNPs might have a toxic effect on the uterine features of mice. In this study, we have investigated the potential effects of CuNPs on the uterus of mice both in vivo and in vitro. In in vivo study, two groups of female mice were exposed to 5 and 50 mg/kg/day via oral exposure. In vivo results showed that CuNP treatment decreases the body weight and uterus weight and changes in antioxidant status with low estrogen and progesterone levels. Furthermore, CuNPs up-regulated the expression of caspase3 and down-regulated the expression of apelin receptor (APJ). Immunolocalization of apelin showed low abundance in the CuNP-treated uterus. These results suggest a poor apelin signaling in the uterus after CuNP treatment. The in vivo findings were further supported by the in vitro studies. Firstly, the uterus was cultured with 5 and 40 μg of CuNPs, and in the second in vitro experiment, the uterus was divided into 4 groups: control, 40 μg of CuNPs, 40 μg of CuNPs with apelin, and 40 μg of CuNPs with apelin receptor antagonist (ML221). In vitro study showed that CuNPs could directly induce the oxidative stress and apoptosis as well as changing antioxidant status in the uterus. The in vitro apelin 13 (APLN 13) treatments alleviated the expression of BCL2 and improved the antioxidant markers in CuNP-treated uterus. These results also provided an evidence of apelin-mediated signaling in the CuNP-treated uterus. In summary, our results present evidence that CuNPs can stimulate apoptotic pathways which may lead to uterine impairment due to weak apelin signaling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)