Anaplastic thyroid cancer: Pathogenesis, prognostic factors and genetic landscape (Review).

Anaplastic thyroid cancer (ATC) is a rare and aggressive form of thyroid malignancy, presenting significant challenges in diagnosis and treatment. The rarity of this cancer and its aggressive nature make an accurate diagnosis difficult, requiring a multidisciplinary approach and various imaging techniques. Treatment involves a personalized multimodal approach, including surgery, adjuvant therapies and risk stratification. Prognostic factors such as age, tumor characteristics and genetic alterations play a crucial role in determining patient outcomes. Despite advancements, gaps remain in understanding the underlying mechanisms of the disease and establishing standardized treatment guidelines. Further research, collaborative efforts and multicenter studies are necessary to improve diagnostic accuracy, develop targeted therapies and biomarkers, and enhance the long-term management. The present review provides a comprehensive overview of ATC, discussing its clinical manifestations, diagnostic approaches, treatment options, prognostic factors and genetic landscape.

Changes in BMD T-score from pre-to post-treatment with biosimilar teriparatide: A single-arm, multi-center study.

Introduction: Teriparatide is a recombinant analog of the parathyroid hormone and an anabolic treatment modality for osteoporosis. This study aimed to evaluate the effectiveness of biosimilar teriparatide (CinnoPar®, CinnaGen Co., Iran) in osteoporotic patients after at least one year of treatment. Methods: In this multi-center, single-arm study, 239 eligible patients received subcutaneous injections of biosimilar teriparatide 20 µg once daily for at least one year. The main outcome measure was the change in bone mineral density (BMD) T-score from baseline (pre-treatment) to end of the study (post-treatment). In addition, the change in the fracture risk assessment tool (FRAX) score was calculated to estimate the 10-year probability of major and hip fractures pre-and post-treatment. Results: A total of 239 patients (age, 63 ± 12.14 years; female, 88.28 %) were included, of which 27.62 % (66/239), 14.64 % (35/239), and 57.74 % (138/239) received biosimilar teriparatide for 12-16 months, 17-20 months, and 21-24 months, respectively. From baseline to end of the study, the T-score at the lumbar spine increased from -2.67 ± 1.04 to -2.26 ± 1.11 (mean percent change, 13.07 ± 62.89; p-value<0.001). Similarly, the T-score at femoral neck increased from -2.18 ± 0.87 to -2.09 ± 0.93 (mean percent change, 3.81 ± 31.52; p-value = 0.006). The proportions of patients with maintained or improved BMD T-score at the lumbar spine and femoral neck sites were 85.36 % (204/239) and 69.04 % (165/239), respectively. Similar results were obtained in subgroups of patients with rheumatoid arthritis and those with a history of a previous fracture or parental hip fracture. FRAX scores did not change significantly during the study (p-values of 0.551 and 0.973 at the lumbar spine and femoral neck, respectively). Conclusion: We observed considerable improvements in BMD following treatment with the biosimilar teriparatide for one year or more. The biosimilar teriparatide can be considered as an effective treatment option in female and male patients with osteoporosis.

Local Delivery of Azithromycin Nanoformulation Attenuated Acute Lung Injury in Mice.

Humanity has suffered from the coronavirus disease 2019 (COVID-19) pandemic over the past two years, which has left behind millions of deaths. Azithromycin (AZ), an antibiotic used for the treatment of several bacterial infections, has shown antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as against the dengue, Zika, Ebola, and influenza viruses. Additionally, AZ has shown beneficial effects in non-infective diseases such as cystic fibrosis and bronchiectasis. However, the systemic use of AZ in several diseases showed low efficacy and potential cardiac toxicity. The application of nanotechnology to formulate a lung delivery system of AZ could prove to be one of the solutions to overcome these drawbacks. Therefore, we aimed to evaluate the attenuation of acute lung injury in mice via the local delivery of an AZ nanoformulation. The hot emulsification-ultrasonication method was used to prepare nanostructured lipid carrier of AZ (AZ-NLC) pulmonary delivery systems. The developed formulation was evaluated and characterized in vitro and in vivo. The efficacy of the prepared formulation was tested in the bleomycin (BLM) -mice model for acute lung injury. AZ-NLC was given by the intratracheal (IT) route for 6 days at a dose of about one-eighth oral dose of AZ suspension. Samples of lung tissues were taken at the end of the experiment for immunological and histological assessments. AZ-NLC showed an average particle size of 453 nm, polydispersity index of 0.228 ± 0.07, zeta potential of -30 ± 0.21 mV, and a sustained release pattern after the initial 50% drug release within the first 2 h. BLM successfully induced a marked increase in pro-inflammatory markers and also induced histological changes in pulmonary tissues. All these alterations were significantly reversed by the concomitant administration of AZ-NLC (IT). Pulmonary delivery of AZ-NLC offered delivery of the drug locally to lung tissues. Its attenuation of lung tissue inflammation and histological injury induced by bleomycin was likely through the downregulation of the p53 gene and the modulation of Bcl-2 expression. This novel strategy could eventually improve the effectiveness and diminish the adverse drug reactions of AZ. Lung delivery could be a promising treatment for acute lung injury regardless of its cause. However, further work is needed to explore the stability of the formulation, its pharmacokinetics, and its safety.

Three Siblings With Woodhouse-Sakati Syndrome: A Case Report of A New Saudi Family.

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive multi-system genetic disease caused by loss of function mutations in the DCAF17 gene on chromosome 2q31.1. The disease is characterized by gradual neurologic degeneration and polyendocrinopathy, particularly noteworthy for hypogonadism, beginning in early adolescence. Clinical features show wide variability with no clear genotype-phenotype correlation. The pathophysiology of WSS is unclear at present and no specific treatment is available other than hormone replacement which is administered in the course of individualized symptomatic multidisciplinary care. Genetic testing helps in confirming the diagnosis along with genetic counseling of the patient and family members. Here we report multiple cases of WSS in three siblings from a new Saudi Arabia family who were diagnosed with WSS as a consequence of a common founder mutation in the DCAF17 gene with DNA analysis showing a homozygous single nucleotide frameshift deletion (c.436delC) in exon 4 of the gene.

The role of forskolin as a lipolytic stimulator during in vitro oocyte maturation and the in vitro embryo production of livestock.

Cryopreservation is a modern technique which assists in the preservation of genetic material from oocytes and embryos for a long time. However, elevated vulnerability to cryopreservation due to the large accumulation of intracellular lipids within oocytes or embryos avoids success of this method. These lipids remain the main crucial factor limiting survival rates of oocytes and embryos after thawing. Lipid ingathering in the oocyte cytoplasm augments lipid peroxidation (LPO) and oxidative stress increases the apoptosis process, declines the viability after thawing, declines cytoskeleton actin filament injuries, lowers the blastocyst rates and reduces cryotolerance in the early stages of embryo development. There have been several attempts to reduce the ingathering of intracellular lipids in oocytes or embryos during the cryopreservation process, in that way enhancing the competence of cryopreserved oocytes or embryos and increasing their viability. One of the most applied agents for chemical delipidation is forskolin. Forskolin exhibited a possible part in improving the oocytes cryopreservation through stimulating cyclic adenosine monophosphate (cAMP) production. The main purpose of cAMP modulation is to provide energy to sustain the mammalian oocytes´ meiotic arrest. The purpose of the existing article is to assess and offer more evidence concerning the forskolin utilization as a modulator of cAMP during the cryopreservation of oocytes and its influence on meiosis completion and the reorganization of cytoplasm, which are prerequisites for the development of oocytes in addition to the contribution to fertilization and subsequently, the development of embryos.

Pomegranate juice reverses AlCl3-Induced neurotoxicity and improves learning and memory in female mice.

BACKGROUND: Aluminum is a neurotoxic element that can accumulate in the brain and cause neurodegenerative disorders. In addition, the antioxidants found in pomegranate juice (PJ) are much more than those existing in other fruits. It was proven to provide protection against neurodegenerative diseases. OBJECTIVES: This experiment aimed to clarify the amelioration efficiency of PJ against aluminum chloride-induced neurobehavioral and biochemical disorders in female mice. METHODS: The female mice were given oral administrations for 35 days as follows. The control group received tap water, the PJ groups received 20% and 40% pomegranate juice, the aluminum chloride (AlCl3) group was treated with 400 mg/kg AlCl3, and the last two groups received AlCl3 + 20% PJ and AlCl3 + 40% PJ, respectively. The neurobehavioral features were assessed by shuttle box, T-maze, and Morris water maze devices. Furthermore, the neurotransmitters and oxidative indicators in the brains of the female mice were determined at the end of experiment. RESULTS: Significant effects of AlCl3 were observed on female mice in the body weight, during the behavioral tasks (shuttle box, T-maze, and Morris water maze), and in neurotransmitters and oxidative stress parameters. Pomegranate juice, especially at low concentrations, induced remarkable improvements in body weight, spatial memory and learning during T-maze, Morris water maze and shuttle box tasks, as well as in neurotransmitters and oxidative biomarkers in the AlCl3-treated female mice. CONCLUSION: PJ reversed AlCl3-induced neurotoxicity and improved learning and memory in female mice. However, PJ contains a group of antioxidants that may be considered double-edged swords in the cellular redox status especially at high doses.

The in vitro development of cloned sheep embryos treated with Scriptaid and Trichostatin (A).

Although, it has been success in the generation of animal clones from somatic cells in various animal species, the information related to nuclear reprogramming of cloned embryos is found to be limited. This study aims to compares the effect of both Scriptaid (SCR) and Trichostatin (A) treatments in improving cloning efficiency, and embryos developmental rate of cloned sheep embryos in vitro. Three groups were formed, i.e., one SCR group, second TSA group, with both treatment concentrations of 5 nM, 50 nM, and 500 nM, respectively, and third were control group with 0 nM. Methods: Ovaries of slaughtered sheep were collected and oocytes were recovered from antral follicles using aspiration method and in vitro maturation of oocytes were done. Then zona dissecting with micropipettes and oocyte enucleation were carried out under the micromanipulator. Later nuclear transfer, cell fusion and activation were done via cell fusion machine. Finally the embryo cultured in incubating chamber at the CO2 incubator up to 9 days. The result: In general the results showed that when the concentration increases the cleavage rate increased. The cleavage rates of the SCNT embryos treated with SCR at different concentrations are closely related to cleavage rate of embryos treated with TSA at same concentration; such as 39.47% for 500 nM TSA, 38.09% for 500 nM SCR; 18.6% for 50 nM TSA, 19.17% for 50 nM SCR, and 22.64% for 5 nM TSA, 17.18% for 5 nM SCR. As for the control group, the cleavage rate of the SCNT embryos cleavage ratewere27.47%., 30% and 30.85% respectively for bothtreatments. While there is a significant difference in TSA treatments at an eight-cell stage at the concentration (5 and 50 nM TSA) compared to the all other cleavage cell stages of (500 nM TSA and control). Also their were a differences between (50 nM of TSA) compared to the (50 nM SCR). Also there were a significant differences between the 16 cell stage at the (500 nM TSA) compared to other treatment (5 nM, 50 nM TSA and control). Regarding the SCR there were a significant difference at 8 cell stage between (5 nM SCR), compared to the other treatment (50 nM, 500 nM SCR and control). Also there were a significant difference at 16 cell stage between (50 nM, and 500 nM SCR), compared to the other treatment (5 nM SCR and control). While in the development of the embryos reach to blastocyst stage the SCR and the control group show a higher rate, in compered to TSA that did not show any development to blastocyst stage. The total SCR treatment showed (3/41 = 7.31%), and the total control showed (4/89 = 4.49%) blastula stage. It concludes that SCR improve the final development blastula stage compared to the TSA treatments that did not improved embryos reach to final developmental blastula stages may be due to spices differences or to the toxicity of TSA, especially at higher concentrations.

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice.

OBJECTIVE: Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. METHODS: C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. RESULTS: DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3 ± 0.4 CD vs. 1.4 ± 0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0 ± 0.6 CD vs. 1.5 ± 0.2 DHA), IL-1ß (60.7 ± 7.0 CD vs. 11.6 ± 1.9 DHA), and IL-10 (223.8 ± 62.1 CD vs. 135.5 ± 38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/ß myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8 ± 11.5 CD vs. 78.8 ± 13.6 DHA) but terminated earlier (CCL2 72 h: 39.5 ± 7.8 CD vs. 8.2 ± 1.9 DHA; CCL3 72 h: 794.3 ± 270.9 CD vs. 258.2 ± 57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6 ± 2.6 CD vs. 31.4 ± 1.5 DHA). CONCLUSION: Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to ß-MHC isoform switch.

Anticancer Activity Assessment and DNA Binding Properties of Two Binuclear Platinum (II) Complexes using Spectroscopic and Molecular Simulation Approaches.

BACKGROUND: Nowadays, the biological properties and anticancer activities of platinum-based drugs and metal coordination complexes have been receiving particular attention. These compounds have revealed clinical potential in cancer chemotherapy. OBJECTIVE: In this research, two binuclear platinum complexes including [Pt2Cl2(bhq)2(µ-dppm)] (1) and [(p- MeC6H4)(bhq) Pt(µ-dppm)Pt(bhq)(CF3CO2)] (2) with bhq: benzo[h] quinolone and dppm: bis(diphenylphosphino) methane have been synthesized and evaluated for their anticancer activity against A2780 and A2780/RCIS cancer cell lines. METHODS: The DNA binding and interaction of AMP/GMP nucleotide with these complexes were explored by several experimental and theoretical methods, including UV-Visible, fluorescence spectroscopic techniques and docking analysis. These complexes have demonstrated significant anticancer properties against cisplatinsensitive (A2780) and cisplatin-resistant (A2780/RCIS) human ovarian cancer cell lines. RESULTS: The obtained results indicated that these complexes interact with DNA. Additionally, the fluorescence emission measurements indicated that the platinum complexes binding with DNA structure occurs through nonintercalative interaction. The molecular docking assessments have also revealed the binding of these platinum complexes through DNA grooves. Moreover, the results have indicated that complex 1 exhibited more anticancer activity than complex 2. CONCLUSION: The results of the DNA binding with these platinum complexes confirmed their potential antitumor properties. The substitution of -C6H4CH3 and -CO2CF3 groups in complex 2 with two chlorine atoms in complex 1 acquired the significant improvement of the anticancer activity against the cancer cell.

Effect of different concentrations of resveratrol on the quality and in vitro fertilizing ability of ram semen stored at 5 °C for up to 168 h.

The aim of the study was to investigate the effects of different concentrations of resveratrol on head morphology, motility characteristics, oxidative state and in vitro fertility of cooled ram spermatozoa. Pooled semen from three Najdi rams was diluted with Triladyl® having different concentrations of resveratrol, zero (control), 200 µM (45.65 µg/mL) and 400 µM (91.30 µg/mL) resveratrol, then stored at 5 °C for 168 h. The head morphometric, sperm kinematic parameters, Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and in vitro fertilizing capability of ram spermatozoa were evaluated after 24, 72, 120 and 168 h of cooling storage. The total motility (TM) of the sperm with resveratrol at 200 µM and 400 µM was significantly (p ≤ 0.05) higher than that in the control group at 72 and 120 h of cooling storage. On the other hand, the progressive motility (PM) of the sperm with resveratrol at 200 µM and 400 µM was significantly (p ≤ 0.05) higher than that in the control group at 168 h of cooling storage period. After 168 h of cooling storage, significantly higher straightness (STR) was observed in 400 µM group than two other groups and in 200 µM group than the control group. Both resveratrol groups had higher linearity (LIN) than control one at 120 and 168 h of cooling storage. The length, width and area of sperm head were lower (P ≤ 0.05) in the control compared to the other treatment groups after 120 and 168 h of storage. There was a significant increase in superoxide dismutase (SOD) concentration in the two resveratrol groups compared with the control one over the seven days of cooling storage and the same result was found in the reduced glutathione (GSH) concentration at 24, 72, and 168 h of storage. There was a significant (p ≤ 0.05) decrease in malondialdehyde (MDA) concentration in the 400 µM resveratrol group than that in two other groups over the seven days of storage period. Cleavage and blastocyst rates following in vitro fertilization were significantly higher (p ≤ 0.05) in 400 µM resveratrol than other groups at 72 h for cooling storage period. In conclusion, addition of resveratrol in the extender can protect sperm head morphology, improve kinematic parameters and in vitro fertility, and reduce oxidative stress of ram spermatozoa during liquid storage at 5 °C.

Immunohistochemistry of IL-1ß, IL-6 and TNF-α in spleens of mice treated with gold nanoparticles.

Gold nanoparticles (AuNPs) possess considerable biocompatibility and therefore gaining more attention for their biomedical applications. Previous studies have shown the transient increase in pro-inflammatory cytokines expression in different organs of rats and mice exposed to AuNPs. Structural changes in the spleen of mice treated with AuNPs have also been reported. This investigation was aimed to study the immunostaining of IL-1ß, IL-6 and TNF-α in mice treated with different sizes of AuNPs. The animals were divided into 7 groups of 4 animals in each group. One group received saline and served as control. Two sets of three groups were treated with 5 nm, 20 nm and 50 nm diameter AuNPs. One set was sacrificed on day 1 and the other on day 7 following the AuNPs injections. Spleens were dissected out and promptly fixed in formalin for 3 days and then processed for IL-1ß, IL-6 and TNF-α immunostaining using target-specific antibodies. The immunoreactivities of IL-1ß and IL-6 were increased with the increase of AuNP size. The immunostaining of IL-1ß in spleen of 20 nm AuNP treated mice was subsequently decreased on day 7 whereas it persisted in 50 nm AuNP group. The increase in the immunoreactivity of IL-6 on day 1 was decreased on day 7 in the spleens of mice treated with 20 nm or 50 nm AuNPs. The immunostaining of TNF-α was found to be negative in all the treatment groups. In conclusion, the size of AuNPs plays an important role in the expression of proinflammatory cytokines in mouse spleen; small size (5 nm) AuNPs caused minimal effect, whereas larger (50 nm) AuNPs produced intense immunostaining.

The Usefulness of Retinoic Acid Supplementation during In Vitro Oocyte Maturation for the In Vitro Embryo Production of Livestock: A Review.

Retinoic acid (RA) is an indigenous metabolite and descriptive physiologically functioning constituent of vitamin A. Retinoids were documented as vital regulators for cell development and distinction, embryonic growth, and reproductive function in both male and female livestock. Previously, RA has been shown to have several positive impacts in vivo and in vitro and critically control many reproductive events, such as oocyte development, follicular growth, and early embryonic growth. In addition, RA manages apoptotic signaling and oxidative damages in cells. Recently, RA has been used widely in assisted reproductive technology fields, especially during in vitro embryo development in various mammalian species, including buffaloes, bovine, goats, sheep, pigs, and rabbits. However, the optimum concentration of RA greatly differs based on the condition of maturation media and species. Based on the obtained findings, it was generally accepted that RA enhances nuclear oocyte maturation, cleavage and maturation rates, blastocyst formation, and embryo development. As such, it possesses antioxidant properties against reactive oxygen species (ROS) and an anti-apoptotic effect through enhancing the transcription of some related genes such as superoxide dismutase, prostaglandin synthase, glutathione peroxidase, peroxiredoxins, and heme oxygenase. Therefore, the current review concludes that an addition of RA (up to 50 nM) has the potential to improve the oocyte maturation media of various species of livestock due to its antioxidant activity.

Time-Course Evaluation of Iminodipropionitrile-Induced Liver and Kidney Toxicities in Rats: A Biochemical, Molecular and Histopathological Study.

Iminodipropionitrile (IDPN) is known to produce axonopathy and vestibular hair cell degeneration. Recent histopathological studies have shown IDPN-induced liver and kidney toxicities in rodents; however, the associated mechanisms are not clearly understood. We investigated the role of proinflammatory cytokines in IDPN-induced liver and kidney toxicities in rats. Rats were treated with saline (control) and IDPN (100 mg/kg, intraperitoneally) daily for 1, 5, and 10 days, respectively. Animals were killed 24 hours after the last dose and liver and kidneys were collected for histopathology and interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α messenger RNA expression analysis. Serum aspartate aminotransferase and alanine aminotransferase activities were significantly increased after 10 doses of IDPN. The level of serum creatinine was initially increased after the first dose of IDPN but subsided on days 5 and 10. Blood urea nitrogen levels were significantly increased on days 5 and 10 following IDPN exposure. Histopathology showed dose-dependent hepatotoxicity in IDPN-treated rats. Iminodipropionitrile-induced expression of proinflammatory cytokines peaked after day 1 in liver and after day 5 in kidneys. In conclusion, repeated exposure of IDPN for 10 days produced significant structural and functional damages in rat liver whereas kidneys showed gradual recovery with time. These findings point toward the role of inflammatory mediators in IDPN-induced toxicity in rats.

Spirulina consumption effectively reduces anti-inflammatory and pain related infectious diseases.

BACKGROUND: Inflammation and pain triggers several pathological illnesses. Synthetic drugs used for the controlling of inflammatory conditions convey significant toxic effects. Global scientific community continually attempt to improve effective, economic and harmless naturally derived remedies against inflammation and pain. The present study aimed to quantify the phytochemical constituents of the freshly cultivated Spirulina and targeted to examining the anti-inflammatory and analgesic activity of Spirulina extract (SE) derived from Arthrospira platensis. METHODS: The anti-inflammatory effect of SE was evaluated in animal models including carrageenan-induced rat hind paw oedema, and cotton pellet-induced granuloma formation. Analgesic effects of SE were evaluated by acetic acid induced writhing response and hot plate test. RESULTS: Phytochemical quantification guided to identify seven carbohydrates, thirteen amino acids, eleven fatty acids and polyphenolic compounds respectively. The results indicated that SE significantly attenuated carrageenan-induced hind paw oedema, and cotton pellet-induced granuloma. Preliminary molecular mechanistic studies established that SE decreased the productions of TNF-α, IL-1ß, IL-6, PGE2 and NO, and suppressed the activities of COX-2 and iNOS. CONCLUSION: These results provide a strong scientific foundation for the anti-inflammatory and analgesic activities of SE against different studies in animal models.

Betulinic acid lowers lipid accumulation in adipocytes through enhanced NCoA1-PPARγ interaction.

BACKGROUND: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. METHODS: Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. RESULTS: Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. CONCLUSION: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation.

Effect of short artificial lighting and low temperature in housing rooms during non-rutting season on reproductive parameters of male dromedary camels.

Ten dromedary mature males were used to study the effects of short artificial lighting and low temperature on the reproductive behavior, testicular size, semen quality and hormone during the non-rutting season and subsequent rutting season. Bulls were allocated into two groups: the first group were subjected to natural daylight and temperature and used as a control. The second group was housed individually in light and temperature controlled rooms in which artificial light (300 lux) was used for 10 h/d, and the temperature was 25.28 ±â€¯0.21 °C. The trial was initiated in mid-June and continued for 10 weeks in the non-rutting season. The reproductive parameters of all animals in the control and room groups were evaluated once every two weeks. The reproductive parameters of all animals in the control and room groups were re-evaluated during the rutting season of the same year. A significant (P < 0.05) increase in the morphometry of the testes, scrotum, libido, and reaction time score, as well as serum melatonin and testosterone levels, was observed in the treatment non-rutting season (TNRS) group compared to in the control non-rutting season (CNRS) group. The testicular volume, reaction time score, serum melatonin, and testosterone were significantly (P < 0.05) higher in the treatment rutting season (TRS) group than in the control non-rutting season (CRS) group. Improvement in the semen parameters were observed in the TNRS and TRS groups compared to in the CRS group. In conclusion, these results demonstrate that short artificial lighting and low temperature can induce rutting out of season and improve the reproductive parameters of dromedary males during the subsequent rutting season.

Impact of thymoquinone on cyclosporine A pharmacokinetics and toxicity in rodents.

OBJECTIVES: Cyclosporine A (CsA) is an immunosupprsant drug used to prevent graft rejection and in the treatment of several autoimmune diseases. Thyomquinone (TQ), a bioactive component of Nigella sativa, has strong antioxidant properties and has been used in prevention of many toxicities, hence its protective effect and pharmacokinetic interactions with CsA was investigated in this study. METHODS: For bioavailability study, the rats were divided into four groups: TQ (PO, 10 mg/kg) was given alone for 7 days, then TQ plus CsA for another 5 days, CsA was given by two routes (po) and (IP) in a dose of 10 mg/kg 1 h after administration of TQ. Blood samples were taken at the 12th day at specified times, CsA level was determined by immune assays. The protective effect of TQ was studied. Blood samples for lab investigations and histopathology were taken at the 28th day. KEY FINDINGS: Thyomquinone reduced the bioavailability of oral CsA by around 32% (P > 0.05). However, bioavailability of IP administered CsA was not affected. Chronic administration of CsA increased concentrations of fasting glucose and Cystatin C and produced marked s kidney alteration of parenchyma which was reversed by concomitant administration of TQ. CONCLUSIONS: A potential drug interaction between TQ and CsA, which may reduced its oral bioavailability. Independently TQ caused significant attenuation of CsA induced renal toxicity and diabetogenic effect.

Bioconversion of acid- and gamma-ray-treated sweet potato residue to microbial protein by mixed cultures.

Sweet potato residue, a starchy agricultural waste, was used as a substrate to produce microbial protein by Fusarium moniliforme and Saccharomyces cerevisiae in submerged fermentation. Acid- and gamma-irradiation-pretreated sweet potato residue enhanced the biomass yield and protein production when the residue was fermented with F. moniliforme and S. cerevisiae. A mixed culture of F. moniliforme and S. cerevisiae efficiently and rapidly utilized free sugars; the maximal biomass yield (13.96 g/l) and protein production (65.8%) were obtained after 3 days fermentation. Lower carbon utilization by the two microbial strains occurred in the waste-containing media as compared to control, increasing the economic value of the waste usage.

TNF-alpha and homocysteine levels in type 1 diabetes mellitus.

The role of homocysteine as an independent risk factor for vascular endothelial damage, and the possible link between homocysteine and tumour necrosis factor-alpha (TNF-alpha) as two synergistic risk factors for beta-cell apoptosis in type 1 diabetes mellitus was studied. Plasma homocysteine levels were significantly elevated in all diabetic patients compared with controls and diabetic patients with vascular complications showed higher elevations. Furthermore, homocysteine levels showed significant positive correlation with the degree of microalbuminuria. TNF-alpha levels were elevated in all diabetic patients compared with controls. These results may have therapeutic implications.

Prevalence of infertility in rural areas of Kafr El-Sheikh-Egypt: a community-based study.

The current study was carried out in Desok district-Kafr El Sheikh province, to measure the prevalence of primary and secondary infertility among rural women and to study some risk factors as well. The study included 1125 married women between 15-49 years. The results of the study showed that; 7.9% reported secondary infertility 2.5% experienced primary infertility, the prevalence of primary infertility is higher among women under 30 years than older ages, and secondary infertility increases with advance in age. Both types of infertility were higher among women married under the age of 16 or above 30 years. There was an insignificant difference between fertile group and infertile groups regarding age at menarche. Irregular menses was significantly higher among infertile groups compared to fertile group. Secondary infertility group had significant higher abortion and difficult labor than fertile group. There was an insignificant difference between the study groups regarding illiteracy rate. Chronic illnesses of women as well as husbands were significantly more reported among women with secondary infertility. In conclusion, the overall prevalence of infertility is 10.4 %.