Proteasome activity contributes to pro-survival response upon mild mitochondrial stress in Caenorhabditis elegans.

Defects in mitochondrial function activate compensatory responses in the cell. Mitochondrial stress that is caused by unfolded proteins inside the organelle induces a transcriptional response (termed the "mitochondrial unfolded protein response" [UPRmt]) that is mediated by activating transcription factor associated with stress 1 (ATFS-1). The UPRmt increases mitochondrial protein quality control. Mitochondrial dysfunction frequently causes defects in the import of proteins, resulting in the accumulation of mitochondrial proteins outside the organelle. In yeast, cells respond to mistargeted mitochondrial proteins by increasing activity of the proteasome in the cytosol (termed the "unfolded protein response activated by mistargeting of proteins" [UPRam]). The presence and relevance of this response in higher eukaryotes is unclear. Here, we demonstrate that defects in mitochondrial protein import in Caenorhabditis elegans lead to proteasome activation and life span extension. Both proteasome activation and life span prolongation partially depend on ATFS-1, despite its lack of influence on proteasomal gene transcription. Importantly, life span prolongation depends on the fully assembled proteasome. Our data provide a link between mitochondrial dysfunction and proteasomal activity and demonstrate its direct relevance to mechanisms that promote longevity.

Assessment of Toxicity of Green Synthesized Silver Nanoparticle-coated Titanium Mini-implants with Uncoated Mini-implants: Comparison in an Animal Model Study.

AIM: To assess the potential for systemic toxicity when silver nanoparticle-coated mini-implants were implanted in Wistar albino rats conducted as a comparative study in the animal model by assessing the blood biochemistry, liver and kidney function, and histology of the implanted site. MATERIALS AND METHODS: The surface of the mini-implant was coated with a green-mediated silver nanoparticle. Uncoated mini-implants were placed in two groups of eight Wistar albino rats, and silver nanoparticle-coated mini-implants were placed in another eight rats. The bone's general conditions, blood biochemistry assessing for ALT, AST, GPT, GOT, and histological sections using H and E stain and Masson's Trichrome stain were examined at 7, 14, and 28-day intervals. RESULTS: The creatinine, urea, ALP, and ALT showed no signs of systemic toxicity during the 28-day follow-up period in the Wistar rats both in the test and control groups. The histological evaluation, which was conducted using HE and MTS stain, revealed osteogenesis and adequate healing of the insertion site in the group where coated mini-implant was placed. The bone sample revealed no abnormalities in the control group with uncoated mini-implants. CONCLUSION: Green synthesized silver nanoparticle-coated mini-implant does not cause systemic toxicity as indicated by no abnormalities in the levels of creatinine, urea, ALT, ALP, GPT, and GOT. The bone histology indicates that the coated mini-implants placed in animal bone healed with adequate osteogenesis. CLINICAL SIGNIFICANCE: Silver nanoparticles have potential for antimicrobial activity. Mini-implants placed as temporary anchorage devices in orthodontics often fail due to inflammation and plaque. Silver nanoparticle-coated mini-implants would reduce the risk of mini-implant failure as it would have antimicrobial potential and eliminate this cause for failure of mini-implants. How to cite this article: Sreenivasagan S, Subramanian AK, Mohanraj KG, et al. Assessment of Toxicity of Green Synthesized Silver Nanoparticle-coated Titanium Mini-implants with Uncoated Mini-implants: Comparison in an Animal Model Study. J Contemp Dent Pract 2023;24(12):944-950.

Mitochondrial control of cellular protein homeostasis.

Mitochondria are involved in several vital functions of the eukaryotic cell. The majority of mitochondrial proteins are coded by nuclear DNA. Constant import of proteins from the cytosol is a prerequisite for the efficient functioning of the organelle. The protein import into mitochondria is mediated by diverse import pathways and is continuously under watch by quality control systems. However, it is often challenged by both internal and external factors, such as oxidative stress or energy shortage. The impaired protein import and biogenesis leads to the accumulation of mitochondrial precursor proteins in the cytosol and activates several stress response pathways. These defense mechanisms engage a network of processes involving transcription, translation, and protein clearance to restore cellular protein homeostasis. In this review, we provide a comprehensive analysis of various factors and processes contributing to mitochondrial stress caused by protein biogenesis failure and summarize the recovery mechanisms employed by the cell.

Therapeutic potential of Mucuna pruriens (Linn.) on ageing induced damage in dorsal nerve of the penis and its implication on erectile function: an experimental study using albino rats.

OBJECTIVE: To study the effect of ethanolic seed extract of Mucuna pruriens on damaged dorsal nerve of the penis (DNP) in aged rat in relation to penile erection. METHODS: The rats were divided into four groups Young (3 months), Aged (24 - 28 months), Aged + M. pruriens, and Young + M. pruriens (200 mg/kg b.w/60 days) and were subjected to the hypophysial - gonadal axis, nerve conduction velocity (NCV), and penile reflex. DNP sections were stained with nitric oxide synthase (nNOS), nicotinamide adenine dinucleotide phosphate (NaDPH) diaphorase, androgen receptor (AR), and osmium tetroxide. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining, electron microscopy(EM) and histometric analyses were done. RESULTS: Significant disturbance in hypophysial - gonadal axis was noted in aged rat. With reduced number of myelinated fibers, diameter, vacuolization, indentation of the myelin sheath, and degeneration. nNOS and its cofactor (NaDPH diaphorase) were reduced in aged rat DNP. NCV was slow in aged rats and concomitant poor penile reflex was also noted. AR showed reduced expression in aged rat DNP when compared to young and control groups. TUNEL positive cells were increased in aged rat DNP. These pathological changes were remarkably reduced or recovered in M. pruriens treated aged rats. CONCLUSIONS: The results indicate a multi-factorial therapeutic activity in penile innervations towards sustaining the penile erection in the presence of the extract in aged rats and justifying the claim of traditional usage.

Histologic Assessment of a Fast-Set Mineral Trioxide Aggregate (MTA) and Two Novel Antibacterial-Enhanced Fast-Set MTAs for Apexification and Periapical Healing of Teeth With Incomplete Root Formation in a Rat Model: An In Vivo Animal Study.

Background Pulp necrosis in incomplete root formation halts dentine development, resulting in larger canals with fragile walls and an open apex, complicating canal instrumentation and apical stop formation. Bioactive endodontic cements such as mineral trioxide aggregate (MTA) are crucial for creating artificial apical barriers or inducing apical foramen closure, but challenges remain regarding their antimicrobial efficacy and cytotoxicity. Modifications to MTA formulations aim to address these concerns. Methods This in vivo animal study involved 80 Wistar albino rats, with incomplete root formation induced by pulp exposure. Rats were divided into four groups receiving different MTA formulations for apexification: conventional MTA, modified MTA, and MTA enhanced with metronidazole or doxycycline. Histopathological evaluations were conducted at seven and 28 days post-treatment to assess calcific barrier formation, inflammatory reactions, and antimicrobial efficacy. Results By day 7, modified MTA formulations exhibited enhanced antibacterial activity compared to conventional MTA (p = 0.000), with fewer inflammatory reactions and microorganisms. By day 28, modified formulations showed superior calcific barrier formation, particularly in the metronidazole- and doxycycline-enhanced groups compared to conventional MTA (p = 0.000). These outcomes suggest that modifications to MTA formulations improve antimicrobial efficacy and calcific barrier formation in vivo. Conclusion Novel modified MTA formulations, particularly those enhanced with metronidazole or doxycycline, exhibit superior antibacterial efficacy and calcific barrier formation compared to conventional MTA. Further long-term studies are warranted to validate these findings for potential clinical translation.

Role of individual and combined impact of simvastatin and α-TCP in rat calvarial bone defect: An experimental study.

Background: Bone substitutes have been used by doctors for a long time to treat osseous abnormalities. Recently, scientists have been searching for suitable materials to replace bone. Autogenous bone grafts are considered the gold standard for osseous regeneration. However, the limited availability of intraoral sources for grafting material often requires the use of secondary donor sites. Aim: This study aims to compare a control group of standard critical bone defect models treated without any bone transplants to critical size calvarial bony defects treated with various bone replacements, including simvastatin and α-tricalcium phosphate, while analyzing the healing patterns. Materials and Methods: In this investigation, 24 Wistar Albino rats weighing 200-250 g were utilized. The study included four groups, each consisting of six rats. Group I utilized deproteinized bovine xenograft, Group II used Simvastatin (0.1 mg), Group III used Simvastatin (0.1 mg) plus TCP, and Group IV served as the untreated calvarial defects group. After eight weeks of testing, the rats were euthanized, and the calvaria were extracted, decalcified in 20% formic acid, and prepared for histological analysis. Results: The newly produced osseous tissue consisted of woven and lamellar bone, which was observed in all deformities. The mean widths of new bone development in the SIMV with α-TCP (Group III) group after XENO (Group I) and the control group with no graft implantation were 160.33 ± 16.2 µm, 110.59 ± 11.5 µm, and 50.83 ± 5.5 µm, respectively. However, these differences did not show statistical significance (p > 0.05). Conclusions: The quantity and quality of newly produced osseous tissue were comparable in α-TCP with SIMV and XENO. However, inflammatory infiltration was 8more pronounced in regions where SIMV was present alone compared to the combination group.

Aging induced testicular damage: analyzing the ameliorative potential of Mucuna pruriens seed extract.

Mucuna pruriens Linn. (M. pruriens), a leguminous plant, was used extensively in Ayurveda, to treat male-related infertility. Previous studies have demonstrated antioxidant, androgenic, aphrodisiac, and spermatogenic properties of M. pruriens seed extract. Surprisingly, the biological activities of M. pruriens on aging-induced pathological changes in the testis microenvironment have never been explored and the present study was focused on the testing therapeutic efficacy of M. pruriens on aged rat testis. Male Wistar albino rats were grouped as; adult (3 months), aged (24 months), aged + M. pruriens and adult + M. pruriens (N = 6/group). The extract was administrated at a dose of 200 mg/kg body weight (dosage determined in our previous study) daily by gavage for 60 days. The total and free testosterone, FSH and LH levels were considerably increased in aged + M. pruriens. The diameter & volume of the seminiferous tubules, the height & volume of the epithelium, and the number of Leydig cells number were significantly decreased in aged rat testis, concomitantly connective tissue proportion was increased compared to adult rats. The seminiferous epithelium indicates significant rejuvenation or restoration of spermatogenic cells in aged + M. pruriens rat testis. The highlighting observations in aged + M. pruriens was increased in the following parameters i.e., tubular diameter (25%), number of tubules (35%), epithelial height (25%) & volume (20%), and number of Leydig cells (35%) when compared to untreated aged rat testis. The TNFα, NF-κB, cytochrome c, Caspase-9, Caspase-3, Bcl-2, Bax, PARP iNOS, and inflammatory and apoptotic factors were downregulated in aged + M. pruriens. M. pruriens was able to restore spermatogenesis and enhance the activity of Sertoli cells and Leydig cells and improve the pituitary-gonadal axis in aged rat testis and observations indicate the therapeutic activity of M. pruriens in aged rat testis.

Morphometric analysis of Bonwill's triangle and its dental applications in dry human mandible bones.

Bonwill's triangle is an imaginary equilateral triangle formed when the centers of two condyles and each condyle with the medial mandibular incisal midpoint are joined. The dimensions of the tooth, with other bones of cranium, and the entire anatomical structure of body are in persistent association with the distance of the borders of the triangle. It can be used to study articulation of the mandible, complete dentures, and dental occlusion and can be related when treating mandibular fractures. The aim is to analyze the variations in the length of Bonwill's triangle in dry human mandibles and its dental implications. Forty dry human mandibles were taken to carry out this study. Distances between the center of the right condylar process to the inner medial mandibular incisal midpoint (A), the distance between the center of the left condylar process to the inner medial mandibular incisal midpoint (B), and the distance between the centers of right and left condylar process of mandible (C) were measured with the aid of digital vernier caliper. The statistics was evaluated and observed using the statistical analysis software SPSS (Version 20.0) and the mean and standard deviation was calculated. The mean length between right condyle center and medial mandibular incisal midpoint is 97.76 mm, between left condyle center and medial mandibular incisal midpoint is 98.55 mm, and between the right and left condyle centers is 97.39 mm. The values are almost equal to 4 inches. The mandibular measurements serve as an important factor for many clinical conditions especially related to dentistry. The results of this study can be of great significance when treating mandibular fractures and defects.

Morphometric analysis of oculomotor triangle in dry human skulls and its clinical applications.

The oculomotor triangle is denoted as the "Triangle of Hakuba" or the "Hakuba's Triangle." This oculomotor triangle is a significant anatomical landmark. Oculomotor nerve, abducens nerve and part of the internal carotid artery (ICA) lie in this triangle. The determination of this analysis is to calculate the oculomotor triangle in dry processed skull bones of the south Indian population and its clinical significance. Fifty-one processed skulls of human origin were received from Anatomy Department, Basic Medical Sciences, Saveetha Dental College. Length from anterior-clinoid process (ACP) to posterior-clinoid process (PCP), length from PCP to APEX, and length from ACP to APEX were measured. Paired samples t-test was considered to analyze the values between the right triangle with the left triangle. From the measurements taken, the mean for the left side of the oculomotor triangle, ACP to PCP was 8.0591 ± 0.52 mm and the right side was 7.5482 ± 0.52 mm. The mean left side of the oculomotor triangle, measured from PCP to APEX was 6.73 ± 0.48 mm and the right side was 6.55 ± 0.72 mm. The mean of the left side of the oculomotor triangle, measured from ACP to APEX was 15.94 ± 0.682 mm and the right side was 16.21 ± 0.747 mm. Through this paired triangle of the cranial cavity, the horizontal section of ICA may be correlated with numerous vascular-related pathological considerations.

Therapeutic potential of Mucuna pruriens (Linn.) on high-fat diet-induced testicular and sperm damage in rats.

Objective: Mucuna pruriens Linn., a leguminous plant, is identified as a herbal medicine for improving fertility-related disorders in the alternative and complementary systems of medicine. The study was focused on evaluating the therapeutic potential of M. pruriens on testis and sperm parameters in a high-fat-induced hypercholesterolemia model. Materials and Methods: Male rats were divided as normal-control rats (NCR); normal-control rats + M.pruriens (200 mg/kg b.w. of ethanolic extract of M. pruriens seed) treated (NCRD); hypercholesterolemic rats (HCR) and hypercholesterolemic rats + M. pruriens (HCRD). Groups were further divided into three post-exposure periods (subgroups) of 9, 18, and 36 days, and the progressive changes in testis histology and sperm were analyzed. Results: The study showed a significant impairment in testicular histoarchitecture, depletion of antioxidant enzyme levels, increased oxidative stress and lipid peroxidation in the HCR group. The study indicated severe structural and functional damage in sperm parameters and diminished chromatin integrity in the HCR group. In the HCR rats, the follicular stimulating hormone (FSH) and luteinizing hormone (LH) and testosterone were significantly reduced. There was a significant improvement in sperm parameters and testis histology in the HCRD group. Conclusion: The study reveals the potential efficacy of M. pruriens to improve spermatogenesis, sperm parameters and hormone levels in hypercholesterolemic rats.

Efficacy of Graphene-Based Nanocomposite Gels as a Promising Wound Healing Biomaterial.

The development of biocompatible nanocomposite hydrogels with effective wound healing/microbicidal properties is needed to bring out their distinguished characteristics in clinical applications. The positive interaction between graphene oxide/reduced graphene oxide (GO/rGO) and hydrogels and aloe vera gel represents a strong strategy for the advancement of therapeutic approaches for wound healing. In this study, the synthesis, characterization, and angiogenic properties of graphene-based nanocomposite gels have been corroborated and substantiated through several in vitro and in vivo assays. In this respect, graphene oxide was synthesized by incorporating a modified Hummer's method and ascertained by Raman spectroscopy. The obtained GO and rGO were uniformly dispersed into the aloe vera gel and hydrogel, respectively, as wound healing materials. These formulations were characterized via in vitro bio-chemical techniques and were found suitable for the appropriate cell viability, attachment, and proliferation. In addition, in vivo experiments were conducted using male Wistar rats. This revealed that the GO/rGO-based gels stimulated wound contraction and re-epithelialization compared to that of the non-treatment group. From the study, it is suggested that GO/rGO-based aloe vera gel can be recommended as a promising candidate for wound healing applications.

Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) is a novel complex III-specific assembly factor in mitochondria.

Assembly of the dimeric complex III (CIII2) in the mitochondrial inner membrane is an intricate process in which several accessory proteins are involved as assembly factors. Despite numerous studies, this process has yet to be fully understood. Here we report the identification of human OCIAD2 (ovarian carcinoma immunoreactive antigen-like protein 2) as an assembly factor for CIII2. OCIAD2 was found to be deregulated in several carcinomas and also in some neurogenerative disorders; however, its nonpathological role had not been elucidated.  We have shown that OCIAD2 localizes to mitochondria and interacts with electron transport chain (ETC) proteins. Complete loss of OCIAD2 using gene editing in HEK293 cells resulted in abnormal mitochondrial morphology, a substantial decrease of both CIII2 and supercomplex III2+IV, and a reduction in CIII enzymatic activity. Identification of OCIAD2 as a protein required for assembly of functional CIII2 provides a new insight into the biogenesis and architecture of the ETC. Elucidating the mechanism of OCIAD2 action is important both for the understanding of cellular metabolism and for an understanding of its role in malignant transformation.

Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress.

Previous studies demonstrated that cells inhibit protein synthesis as a compensatory mechanism for mitochondrial dysfunction. Protein synthesis can be attenuated by 1) the inhibition of mTOR kinase, which results in a decrease in the phosphorylation of S6K1 and 4E-BP1 proteins, and 2) an increase in the phosphorylation of eIF2α protein. The present study investigated both of these pathways under conditions of short-term acute and long-term mitochondrial stress. Short-term responses were triggered in mammalian cells by treatment with menadione, antimycin A, or CCCP. Long-term mitochondrial stress was induced by prolonged treatment with menadione or rotenone and expression of genetic alterations, such as knocking down the MIA40 oxidoreductase or knocking out NDUFA11 protein. Short-term menadione, antimycin A, or CCCP cell treatment led to the inhibition of protein synthesis, accompanied by a decrease in mTOR kinase activity, an increase in the phosphorylation of eIF2α (Ser51), and an increase in the level of ATF4 transcription factor. Conversely, long-term stress led to a decrease in eIF2α (Ser51) phosphorylation and ATF4 expression and to an increase in S6K1 (Thr389) phosphorylation. Thus, under long-term mitochondrial stress, cells trigger long-lasting adaptive responses for protection against excessive inhibition of protein synthesis.

Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7.

Nuclear and mitochondrial genome mutations lead to various mitochondrial diseases, many of which affect the mitochondrial respiratory chain. The proteome of the intermembrane space (IMS) of mitochondria consists of several important assembly factors that participate in the biogenesis of mitochondrial respiratory chain complexes. The present study comprehensively analyzed a recently identified IMS protein cytochrome c oxidase assembly factor 7 (COA7), or RESpiratory chain Assembly 1 (RESA1) factor that is associated with a rare form of mitochondrial leukoencephalopathy and complex IV deficiency. We found that COA7 requires the mitochondrial IMS import and assembly (MIA) pathway for efficient accumulation in the IMS We also found that pathogenic mutant versions of COA7 are imported slower than the wild-type protein, and mislocalized proteins are degraded in the cytosol by the proteasome. Interestingly, proteasome inhibition rescued both the mitochondrial localization of COA7 and complex IV activity in patient-derived fibroblasts. We propose proteasome inhibition as a novel therapeutic approach for a broad range of mitochondrial pathologies associated with the decreased levels of mitochondrial proteins.

Genotyping of benzimidazole resistant and susceptible isolates of Haemonchus contortus from sheep by allele specific PCR.

Extensive and indiscriminate use of the benzimidazole class of drugs has led to the onset of anthelmintic resistance. In tropical countries like India, Haemonchus contortus is the most pathogenic parasite infecting sheep and goats. The widespread presence of resistant helminths (especially H. contortus) threatens the livestock farming. The use of various drugs has led to single nucleotide polymorphism that causes specific amino acid substitutions in ß-tubulin protein of H. contortus to confer resistance. This emphasizes the need for a survey on the present status of resistance in India. In this study, allele specific PCR was employed to screen the presence of a SNP, a thymine-to-adenine transversion which leads to substitution of amino acid in codon 200 of ß-tubulin gene that is correlated specifically with BZ resistance. Third stage larvae (L3) from pooled faecal cultures of four organized sheep farms served as a source of genomic DNA for identification of H. contortus and further genotype analysis. A total of 1000 larvae was screened, out of which 673 larvae were identified as H. contortus. Among 673 H. contortus larvae, 539 larvae (80 %) were genotyped as homozygous resistant (rr) and remaining 134 (20 %) were heterozygous susceptible (Sr) by allele specific PCR. The concluded resistance status reasons out the failure of anthelmintic drug in treating ruminants. Immediate steps are needed to avoid further aggravation of the problem. Target selective treatment by reviewing the resistance status of individual drugs, appropriate use of anthelmintic drugs and other control strategies will provide a pragmatic option for delaying the further spread of anthelmintic resistance.

The Oxidation Status of Mic19 Regulates MICOS Assembly.

The function of mitochondria depends on the proper organization of mitochondrial membranes. The morphology of the inner membrane is regulated by the recently identified mitochondrial contact site and crista organizing system (MICOS) complex. MICOS mutants exhibit alterations in crista formation, leading to mitochondrial dysfunction. However, the mechanisms that underlie MICOS regulation remain poorly understood. MIC19, a peripheral protein of the inner membrane and component of the MICOS complex, was previously reported to be required for the proper function of MICOS in maintaining the architecture of the inner membrane. Here, we show that human and Saccharomyces cerevisiae MIC19 proteins undergo oxidation in mitochondria and require the mitochondrial intermembrane space assembly (MIA) pathway, which couples the oxidation and import of mitochondrial intermembrane space proteins for mitochondrial localization. Detailed analyses identified yeast Mic19 in two different redox forms. The form that contains an intramolecular disulfide bond is bound to Mic60 of the MICOS complex. Mic19 oxidation is not essential for its integration into the MICOS complex but plays a role in MICOS assembly and the maintenance of the proper inner membrane morphology. These findings suggest that Mic19 is a redox-dependent regulator of MICOS function.

D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague-Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the above-mentioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.

Morphological diversity of sperm: A mini review.

Sperms are highly specialized cells for delivering DNA from male to the ovum. Incredibly, wide degree of diversity in sperm morphology in their basic structures i.e. head, middle piece and tail is found across species. Differences in terms of overall size of the sperm, shape and number of sperm produced are also incredible. One of the key for this variations or diversity in sperm may be associated with female reproductive tract, sperm competition, testicular size and sperm size and number. Establishing a correlation between sperm morphology and factors influencing them is a phenomenal task. In this mini-review these associations and the anatomical and functional adaptations among different from of sperm cells that have evolved to optimize fertilization success are discussed. Nevertheless, explaining these morphological diversities in sperm cells is a challenging question and it seems that evolutionary biologists have only recently engaged in exploring its links and patterns. From the literatures it seems that there is no causal relationship between sperm size and testicular size, however, the accumulated knowledge do indicates evolution of sperm morphology across species has some associations with female reproductive tract, sperm competition and sperm size and number, however interpreting these results for phylogentic correlations should be approached with caution.

Effect of Mucuna pruriens (Linn.) on mitochondrial dysfunction and DNA damage in epididymal sperm of streptozotocin induced diabetic rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens Linn. (M. pruriens) is a leguminous plant that has been recognized as an herbal medicine for improving fertility and related disorders in the Indian traditional system of medicine, however without proper scientific validations. AIM OF THE STUDY: To study the effect of ethanolic seed extract of M. pruriens on mitochondrial dysfunction and the DNA damage in hyperglycemic rat epididymal spermatozoa. MATERIALS AND METHODS: Male Wistar albino rats were divided as control (Sham), diabetes induced [streptozotocin 60 mg/kg of body weight (b.w.) in 0.1M citrate buffer] (STZ), diabetic rats administered with 200mg/kg b.w. of extract (STZ+MP) and normal rats administered with 200mg/kg b.w. of extract (Sham+MP). M. pruriens was administered (gavage) once daily for a period of 60 days. On 60th day animals were sacrificed by cervical dislocation sperm were collected from epididymis and subjected various analysis like antioxidants, ROS, lipid peroxidation (LPO), DNA damage, chromosomal integrity and mitochondrial membrane potential (MMP). RESULTS: Significant reduction in the sperm count, motility, viability and significant increase in the number of abnormal sperm in STZ compared to sham was noticed. STZ rat sperm showed significant increase in LPO and DNA damage. Both the enzymic and non-enzymic were decreased; MMP and the mitochondrial functions were severely affected in STZ group. The diabetic rats supplemented with M. pruriens showed a remarkable recovery in antioxidant levels and reduced LPO with well preserved sperm DNA. MMP and mitochondrial function test were also preserved in STZ+MP rat sperm. CONCLUSION: The present study has clearly demonstrated the potency of M. pruriens to reduce the diabetic induced sperm damage induced by oxidative stress (OS). These observations are encouraging to perform similar studies in human.

D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-kB

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague–Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-alfa (TNF-alfa), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the abovementioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis