Objective:  This study aimed to fabricate a multi-polymeric hydrogel scaffold containing carboxymethyl cellulose, alginate, polyvinyl alcohol, and inulin (CMC/Alg/PVA/Inulin) and investigate its role in the differentiation of sheep fetal bone marrow-derived mesenchymal stem cells (MSCs) into oocyte-like cells, in combination with follicular fluid, granulosa cells, and retinoic acid. Methods:  The hydrogel scaffold was synthesized using freeze-drying and cross-linking with calcium chloride and characterized by FE-SEM, EDX, FTIR, XRD, tensile strength, swelling behavior, and enzymatic degradation assays. MSCs were isolated from sheep fetal bone marrow and confirmed at passage 3 by their differentiation potential into adipocytes and osteoblasts using Oil Red O and Alizarin Red S staining, respectively. Cells were then cultured for 21 days in three independent experiments under control conditions (2D), on the scaffold (3D), and on the scaffold with 10 µM retinoic acid. Differentiation media included follicular fluid, granulosa cells, or their combination. Viability and apoptosis were assessed by Alamar Blue and acridine orange/ethidium bromide staining, respectively. The expression of germ cell-specific markers (DDX4, DAZL, and ZP3) was evaluated by real-time PCR. Results:  FE-SEM images revealed a porous structure, and FTIR and XRD analyses confirmed the successful formation of the hydrogel. The scaffold was biocompatible (maximum swelling at 72 hours and 63% degradation by day 21), and retinoic acid showed no significant cytotoxicity at lower concentrations. In all experiments, 3D culture on the scaffold with retinoic acid significantly increased the expression of DDX4, DAZL, and ZP3 compared to 2D and 3D cultures without retinoic acid (p<0.05). The highest expression levels were observed in the co-culture of MSCs with granulosa cells in the combined presence of follicular fluid and retinoic acid on the scaffold. Conclusion:  The CMC/Alg/PVA/Inulin hydrogel scaffold provides a biocompatible and effective 3D substrate for differentiating sheep fetal bone marrow MSCs into oocyte-like cells. The combination of this scaffold with retinoic acid and follicular factors, particularly co-culture with granulosa cells and follicular fluid, significantly enhances differentiation efficiency. This approach offers a novel perspective in reproductive biotechnology and the treatment of infertility in valuable livestock and endangered species.

   Gastric cancer is one of the most prevalent malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality worldwide. The limitations of conventional therapies, including systemic toxicity and drug resistance, highlight the need for novel therapeutic strategies. In the present study, solid lipid nanoparticles (SLNs) were developed as a drug delivery system for the bioflavonoid luteolin, and their anticancer effects were evaluated in human gastric cancer AGS cells. SLNs and luteolin-loaded SLNs were synthesized and characterized in terms of particle size, polydispersity index, zeta potential, and morphology. In vitro drug release behavior was investigated under different pH conditions. The biological effects of the formulations were assessed using MTT assay, intracellular reactive oxygen species (ROS) measurement, qualitative and quantitative apoptosis analysis, and cell cycle evaluation. The results demonstrated that luteolin-loaded SLNs exhibited appropriate nanoscale size, good stability, and a controlled, pH-dependent drug release profile. Blank SLNs showed no significant cytotoxicity, indicating good biocompatibility. Whilst, luteolin-loaded SLNs significantly reduced cell viability, induced controlled ROS generation, enhanced apoptosis, and disrupted cell cycle progression, particularly by inducing S-phase arrest, compared to free luteolin. Overall, these findings suggest that luteolin-loaded solid lipid nanoparticles represent a promising and effective drug delivery system for improving gastric cancer therapy. Keywords: Gastric cancer, Luteolin, Solid lipid nanoparticles, Apoptosis, Cell cycle

Background and Aim: The interaction of drugs and nanodrugs with biological macromolecules such as human serum albumin (HSA) and DNA plays a crucial role in their stability, bioavailability, and therapeutic efficacy. Previous studies have shown that deferoxamine, in addition to its clinical applications as an iron chelator, exhibits notable anticancer effects, and nanostructuring can enhance its stability and biological performance. The aim of this study was to investigate the interactions of free deferoxamine and its iron oxide nanoparticle form with HSA and calf thymus DNA, and subsequently to evaluate their anticancer effects on gastric cancer cells.    Materials and Methods: The interactions of the drug and nanodrug with HSA and calf thymus DNA were analyzed using UV–Vis spectroscopy, fluorescence spectroscopy, and circular dichroism (CD). Molecular docking studies were also performed to determine precise binding sites. Cellular assays, including MTT, intracellular ROS measurement, cell cycle analysis, and apoptosis evaluation, were conducted to assess anticancer effects on gastric cancer cell lines.    Results: Spectroscopic and molecular docking results indicated that both compounds bind to the warfarin site on HSA and preferentially interact with the minor groove (Hoechst site) of DNA. CD spectra revealed an increase in the ?-helix content of HSA in the presence of both compounds, while structural disorder was induced in DNA. Cellular assays demonstrated significant reductions in cell viability, increased ROS production, induction of apoptosis, and cell cycle disruption, with the anticancer effect of the deferoxamine nanodrug being notably stronger than that of the free drug.    Conclusion and Discussion: The results of spectroscopic and docking studies showed that free deferoxamine and its iron oxide nanoparticle form exhibit similar interaction patterns with HSA and calf thymus DNA, binding to the warfarin site in HSA and the minor groove of DNA. Cellular assays further revealed that the nanodrug exerts stronger reductions in cell viability, higher ROS production, greater apoptosis induction, and more pronounced cell cycle disruption in gastric cancer cells, indicating enhanced anticancer effects at the nanoscale.   

  The genus Gammarus is one of the most diverse groups of the order Amphipoda and the class Crustacea. Members of this taxon are widely found in freshwater habitats around the world at mid-latitudes. The aim of this study was to investigate the populations of the genus Gammarus from springs and mirages in Sonqor County in the northeast of Kermanshah Province based on morphological traits. In the present study, five populations were collected from the springs of Lillemanj, Cheshmeh Vakili, Deh Asyab, Charmleh, and Baoleh in the study area. For morphological study, after determining the sex of the specimens, the body parts of the specimens were separated under a loupe with dissecting needles and fixed on a slide containing Euoparal glue. Then, the slides were measured and photographed under a light microscope equipped with a LABOMED iVu 7000 camera, and the different parts of the specimens were drawn using Adobe Illustrator CS6 software. The results of this study confirm the presence of a new species of the genus Gammarus from the Deh Asyab spring and four new records of the species G. anodon from the Lillemanj, Vakili, Charmleh and Baoleh springs based on morphological traits such as the dorsal-posterior angle of epimeral plates I to III, the size and number of filaments on the surface of antenna II, the presence or absence of fine spines on the dorsal surface of the pectoral and abdominal segments, and the shape of caudal segments I to III in the springs of Sonqor County.

  Abstract Stenotrophomonas maltophilia is an increasingly recognised opportunistic pathogenthat is responsible for nosocomial infections in intensive care unit patients, including pneumoniaand ventilator-associated sepsis. It also causes life-threatening diseases in immunosuppressedpatients with haematological malignancies and cancers, and chronic pulmonary infections inpatients with cystic fibrosis (CF). These organisms predominantly cause respiratory tractinfections, with less frequent occurrences of urinary tract infections, wound infections, soft tissueinfections, bacteremia, sepsis, endocarditis, meningitis, eye infections, and peritonitis.In thisstudy, Stenotrophomonas maltophilia strains were isolated from clinical specimens and identifiedby biochemical and fermentation tests. The isolates were then confirmed by polymerase chainreaction using specific primers.Antimicrobial susceptibility tests of the isolates were performed according to the Clinical andLaboratory Standards Institute (CLSI) to the antibiotics ceftazidime, levofloxacin, aztreonam andco-trimoxazole using the disk diffusion method. Subsequently, the presence of the antibioticresistance gene SMqnr and the genes associated with biofilm production rpfF and rmlA wasdetermined using the PCR method. Finally, the biofilm production ability of the antibioticresistant strains carrying the quinolone resistance genes SMqnr and the genes associated withbiofilm production rpfF and rmlA was measured using the microtiter plate method.The highestand lowest susceptibility were to and related to the antibiotics co-trimoxazole and aztreonam,respectively. Furthermore, 51.25% (41) of the isolates demonstrated resistance to the antibioticceftazidime, while the resistance rate to levofloxacin was 75.8% (7 cases).The prevalence of the quinolone antibiotic resistance gene (Smqnr) was 92.5% (74 isolates),and the genes involved in biofilm production (rmIA and rpfF) were found in 98.75% (79 isolates)and 57.5% (46 strains), respectively.With the exception of the presence of the rpfF gene and its association with resistance toceftazidime (p-value < 0.0001) and levofloxacin (p-value < 0.019), no other significantrelationships were observed.All strains in which biofilm production was examined were strong biofilm producers, theminimum biofilm inhibitory concentration of the antibiotic levofloxacin in different strainsranged from 2.5 to 20 ?g/ml, and this amount was lower than that of the antibiotic cefazidime(minimum 20 and maximum 640 ?g/ml).Keywords: antibiotic resistance, biofilm formation, Stenotrophomonas maltophilia, Smqnr

Excessive production of reactive oxygen species (ROS) during freezing and thawing negatively impacts sperm quality and subsequent fertilization capacity. The properties of nanoparticles (with antioxidant properties) have recently gained considerable attention in livestock due to their ability to enhance sperm longevity and improve male fertility. Therefore, the aim of this study was to investigate the effect of adding quercetin, combination of copper chloride and zinc chloride, copper oxide nanoparticles doped with zinc oxide nanoparticles, and quercetin-loaded nanoparticles on doped nanoparticles, on ram sperm quality under post-thaw conditions. Doped nanoparticles were purchased and quercetin was loaded onto them in the laboratory. The characteristics of the nanoparticles were determined using EDX, FE-SEM, UV-visible, FT-IR, and zeta potential. Mixed ejaculates from four Sanjabi rams were diluted with a cryo-preservation extender. Different concentrations of treatments (1, 5, 25, and 125 µg/mL) were added to the ram sperm freezing extender. The control group was considered as the group without any treatment. The semen, diluted and enriched with the above treatments, was gradually cooled to 4°C over 4 hours, then drawn into 0.25 mL straws and frozen in liquid nitrogen for storage. Sperm parameters, such as viability, total motility, membrane and DNA integrity, total abnormalities, and malondialdehyde levels, were assessed in the different groups. The results showed that adding 5 µg/mL copper oxide nanoparticles doped with zinc oxide nanoparticles coated with quercetin significantly increased sperm viability, total motility, membrane and DNA integrity, and decreased malondialdehyde production compared to the control and other treatment groups (p < 0.05). The addition of 5 µg/mL copper oxide nanoparticles doped with zinc oxide nanoparticles coated with quercetin also significantly reduced abnormalities compared to the control and other treatment groups, except for the 25 µg/mL quercetin group (p < 0.05). Therefore, adding 5 µg/mL copper oxide nanoparticles doped with zinc oxide nanoparticles coated with quercetin as an antioxidant to the ram semen extender can improve sperm tolerance to freezing and enhance sperm stability after thawing. Keywords: Sperm, ram, Antioxidant, Quercetin, Copper oxide nanoparticles doped with zinc oxide nanoparticles.   

This study examines antibiotic resistance in Klebsiella pneumoniae isolates in the Middle East up to 2024. The results indicate a concerning increase in resistance to commonly prescribed antibiotics such as beta-lactams and fluoroquinolones, particularly third-generation cephalosporins, which are used to treat serious infections. Additionally, a high prevalence of extended-spectrum beta-lactamases and carbapenemase-producing strains was observed, highlighting the increasing complexity in treating infections. Genomic analyses conducted in this study revealed the molecular mechanisms underlying antibiotic resistance, showing that the transfer of resistance genes and plasmids plays a significant role in the spread of resistance. The emergence of multidrug-resistant strains has limited treatment options and poses a serious threat to the effectiveness of new antibiotics. The findings of this research emphasize the necessity of implementing antimicrobial surveillance programs and infection control measures at the regional level to prevent further spread of resistance. Identifying patterns and key determinants of resistance in the Middle East contributes to a better understanding of the genetic dissemination of resistance and facilitates the development of targeted interventions. These results also pave the way for future research and public health initiatives aimed at addressing this critical global health challenge.   

This study was conducted with the aim of investigating the effect of empagliflozin on the side effects of doxorubicin on the function and tissue structure of rat testis. For this purpose, 28 adult male mice were prepared and divided into 4 groups as follows. Control group: They were kept with the usual diet and without taking any medicine, with other groups. Doxorubicin group: the animals of this group were injected intraperitoneally with doxorubicin at the rate of mg/kg2 on days 1, 7, 14, 21 and 28. The above amount and method were injected, and at the same time empagliflozin was injected daily at the rate of 10 mg/kg intraperitoneally for 28 days. Empagliflozin group: the animals of this group were administered empagliflozin in the above amount and method. After the end of the experiment period, each animal was anesthetized using ketamine and xylazine and blood was taken from the heart. The test tubes containing the blood clot were centrifuged and the serum samples were transferred to the relevant laboratory to measure the sex hormone testosterone and factors related to oxidative stress (MDA, TAC). Also, anesthetized mice were eased without feeling pain, and their right testicle samples were immediately separated and placed in 10% formalin for tissue fixation, and then transferred to the histology laboratory to prepare a tissue slide. Biochemical results showed that in the doxorubicin group, the amount of testosterone hormone and total antioxidant capacity decreased and the amount of MDA increased compared to the control group. Also, in the doxorubicin group, the percentage of non-motile sperms or with non-progressive movement, as well as abnormalities in the head, neck, and tail increased compared to the control group, and the percentage of motile, progressive and normal sperms decreased. In addition, the number of germ cells, the diameter of the spermatogenic tube, and the thickness of its germinal epithelium decreased in the doxorubicin group compared to the control group. In the histological observations, confusion and lack of coherence and tissue order in the arrangement of the seminiferous tubules, complete or local analysis of the tissue corresponding to the germinal covering of the spermatogenic tubules, and the lack of formation and recognition of different sex cells, as well as the relative emptying of the lumen of the tubules from spermatids in the tissue structure of the testis The mice of the doxorubicin group were observed. But treatment with empagliflozin was able to improve all the above adverse changes. Therefore, it seems that empagliflozin can be used to reduce or treat the adverse side effects of doxorubicin in patients undergoing chemotherapy

 Quercetin and thymoquinone are important plant chemical compounds that have various antioxidant, anti-inflammatory and anti-cancer effects by inhibiting different signaling pathways and epigenetic changes. MiRNA are also a group of small non-coding RNAs that, by targeting different genes and affecting signaling pathways, play an important role in regulating gene expression and controlling breast cancer symptoms, and are used as biomarkers for diagnosis, prognosis, and treatment. The aim of this research is to investigate the simultaneous effect of quercetin and thymoquinone on the expression of TSG6, ANO9 genes and their targeting microarrays in MCF-7 breast cancer cells. In this study, MCF-7 cells were cultured and propagated and then treated with different concentrations of quercetin and thymoquinone. After RNA and microarray extraction from cells and cDNA synthesis, using bioinformatics sites including TargetScan, miRBase and miRDB, target microarrays of studied genes were predicted. Also, by using the mentioned sites and the miRNet site, R and Cytoscape software, the best microarrays targeting these genes were predicted for future research. qRT-PCR method was used to quantitatively investigate the expression of genes and microarrays. The results showed that the treatment of MCF-7 cells simultaneously with thymoquinone and quercetin decreases TSG6 gene expression. When the concentration of quercetin or thymoquinone was kept constant, by increasing the concentration of the other substance, the gene expression approached the control group. It is possible that the reduction of TSG6 expression only at the concentration of 35 ?M thymoquinone and 50 ?M quercetin can be affected by hsa-miR-23a-3p, and at other concentrations, it is probably due to the involvement of other pathways and factors. It was also found that with the increase in the concentration of quercetin, the expression of the ANO9 gene decreased significantly at the concentration of 20 ?M thymoquinone, but at the concentration of 35 ?M, the expression of the gene was closer to the control group and also positive. Examining the effect of these two substances on the expression of has-miR-6789-3p, the target of this gene, revealed that increasing the concentration of thymoquinone and quercetin increased the expression, and low concentrations of these two substances decreased the expression of this microarray. It is possible that this microarray targets the ANO9 gene at the concentration of 20 ?M thymoquinone and 50 ?M quercetin. The data showed that the expression of has-miR-154-3p increased with

   Sulfonamides and their derivatives are classical carbonic anhydrase inhibitors (CAIs) currently employed in clinical settings. Much research is centered around enhancing the efficacy of sulfonamide derivatives as potent CAIs. Nevertheless, numerous sulfonamide compounds exhibit no  ecific inhibition of all CA isoforms, leading to reduced drug efficacy and the occurrence of undesirable side effects due to off-target inhibition. Consequently, non-classical CAIs, such as inhibitors that contain carboxylic acid groups, have been employed to selectively target specific isozymes, minimizing adverse effects. In this study, we investigated the interaction between sulfonamide/carboxylic acid derivatives as novel non-classical inhibitors and the hCA II by using various spectroscopic and docking methods. The kinetic data demonstrates that compounds 1 and 2 share a similar inhibitory strength against hCA II, effectively inhibiting its esterase activity through a noncompetitive mechanism with Ki values at low micromolar levels. Fluorescence measurements indicated that the synthesized compounds suppressed the inherent fluorescence of hCA II via a static quenching process, with each compound showing a single binding site within the hCA II structure. A thermodynamic analysis highlights the significance of van der Waals interactions and hydrogen bonds in the binding of these compounds to hCA II. Docking results showed that both compound 1 and compound 2 effectively obstruct the entrance to hCA II's active site, with no significant differences in their binding conformations. While compounds 1 and 2 exhibit CA inhibitory potency lower than that of sulfonamide compounds, this study offers valuable insights that could pave the way for the development of a promising scaffold for designing new CA inhibitors.

  Nowadays, the use of mesenchymal stem cells (MSCs) as a suitable therapeutic method to treat many disorders is increasing and becoming a popular research topic. due to their unique feature in migration, proliferation, differentiation, and immune-modulatory activities These cells have become one of the most used stem cells in recent decades. One of the reasons for the well-received of these cells is their ability to treat immune disorders and repair damaged tissues. In vitro Treating cells with various chemical compounds that seem to be able to amplify the unique feature of mesenchymal stem cells can be a useful approach for the furtherance of medical science. Epigenetics and hypoxia induction play a significant role in guiding mesenchymal stem cells. The purpose of this research is to investigate the effect of sodium butyrate as a compound that causes epigenetic changes (histone deacetylase inhibitor), cobalt II chloride as a hypoxia inducing compound, and also the mixture of these two compounds on the ability to survive, proliferation, migration and immune regulatory effect of mesenchymal stem cells with the In vitro conditions. many studies have been done on the effect of these compounds on other different cells. But so far, no study has been done as this study was conducted on the effect of these two compounds and their mixture on human mesenchymal stem cells. In this study, the effects of different concentrations of sodium butyrate, cobalt II chloride, and the mixture of these two compounds on the survival, proliferation, and production of reactive oxygen species (ROS) of MSCs were measured respectively by MTT, trypan blue, and NBT tests. Further, the effect of these compounds on the cell cycle, cell migration, and the expression of the studied genes were also investigated respectively by flow cytometry, wound healing, and RT-PCR tests. It was observed that sodium butyrate, cobalt II chloride, and the mixture of the two compounds reduce cell survival and increase the level of ROS in mesenchymal stem cells. It was also observed that sodium butyrate stops the cell cycle in the G0/G1 and G2/M phases, cobalt II chloride stops it in the G0/G1 phase and the mixture of the two substances stops the cell cycle in the G2/M and G0/G1 phases. In the following, it was observed that cobalt II chloride has an increasing effect on the migration ability of mesenchymal stem cells, but sodium butyrate and the mixture of these two compounds do not have such an effect. Due to the multiple effects that these compounds have on MSCs. The effect of these compounds was investigated at the molecular level and the expression of TLR3, H19, HIF1?, c-MET, HDAC1, and SOX2 genes was measured under the influence of optimal concentrations of these substances. It was seen that the treatment of mesenchymal stem cells with cobalt (II) chloride increases the expression of TLR3 and H19 genes and decreases the expression of c-MET gene. Also, in the treatment of these cells with sodium butyrate, it was seen that this substance increases the expression of TLR3, H19 and HIF1? genes and decreases the expression of c-MET gene. In the following of this study, it was seen that the treatment of these cells with a mixture of two substances increases the expression of TLR3 and H19 genes and decreases the expression of the c-MET and HIF1? genes. In total, this study shows that all three compounds increase the immune-modulatory property of MSCs, and cobalt (II) chloride plays a significant role in enhancing the migration ability of mesenchymal stem cells.

   Cancer cells consume large amounts of glucose due to their excessive proliferation. Tumors have a high rate of glycolytic pathway which leads to an increase in lactate concentration. The tumor microenvironment contains two types of cancer cells: glycolytic and oxidative cells. Glycolytic cells produce lactate, which is taken up by oxidative cells and converted into pyruvate for use in the Krebs cycle. This forms a metabolic symbiosis between the two cell types. The family of monocarboxylate tra  orters (MCTs) consists of 14 members, with MCT1-4 being proton-coupled tra  orters that can tra  ort short-chain monocarboxylates like lactate and pyruvate across the cell membrane. Cancer cells have high levels of MCT1 and MCT4 expression. MCT1 facilitates lactate influx into oxidative cells, whereas MCT4 is predominantly found in glycolytic cells. Overexpression of these tra  orters has been associated with various malignancies, such as breast, stomach, lymphoma, brain, lung, skin, and soft tissue cancers, making them attractive targets for anticancer drug discovery. By inhibiting MCT1, it is possible to stop oxidative cells from consuming lactate, which will then force them to take up glucose. This process will reduce glucose availability to glycolytic cells and eventually lead to cell death. For this research, we used structure-based virtual screening techniques to discover small chemical compounds capable of inhibiting monocarboxylate tra  orter 1. The atomic coordinates of the protein in the open-inward conformation were obtained from the protein database with the code 7CKO. We utilized a library of chemical compounds which included 12 million molecules that are available for purchase from the ZINC database. Additionally, we included 4683 drugs that have been approved by the FDA. Following library preparation, we utilized a consensus approach by performing molecular docking with AutoDock Vina, Molegro Virtual Docker, and DOCK programs. The ligands possessing high binding energy were subjected to further analysis to determine their interaction with the crucial residues in the protein's binding site. Compounds that showed promising results were subjected to molecular dynamics analysis, including RMSD, RMSF calculations, and analysis of ligand-protein interactions. Based on the findings, it was discovered that enacidnib, an oral medication used to treat acute myeloid leukemia, can create strong binding with important residues such as Tyr 34, Lys 38, and Ser 154 found in the lactate binding site. As a result, it has the potential to effectively inhibit the targeted protein.

  Reproduction is one of the most importante events in an organism lifetime in which the survival and the transfer of genetic pool depend on it. The succsessful maturation of the oocyte is the beging point of this complex process that includes nucleus and cytoplasm maturation. In vitro maturation is an artificial process and aimes to start the oocyte internal mechanisms for completion of maturation in vitro. The essentials for starting, continuing and the completion of oocyte maturation is the availability of energy. This energy is provided by mitochondria and also calcium homeostasis that plays an important role in maturation is controlled by mitochondria as well, but during in vitro culture the gathering of oxidative stress becomes an obsticle for maturation and reduces the oocyte maturation rate. Empagliflozin is an antidiabatic drug with antioxidant properties that through different ways such as improving the energy metabolism, activating the AMPK signaling pathway which is an important signaling pathway in starting the oocyte maturation process, preventing damage to mitochondria, improving calcim homeostasis and providing energy, aides oocyte maturation in vitro. In this research we separated the NMRI 6-8 weeks mice with 27 gage syringe and put the oocytes in 25 microlitter MEM alpha media culture with 50 nanomole, 100 nanomole, 10 micromole and 1 micromole of Empagliflozin doses and incubated them for 24 and 48 houre in an 37 degree, 5% CO2 incubator. After 24 and 48 houre of incubation, we investigated the oocytes under an inver microscope. In order to investigate the results we used Chi-square test. The percentage of maturation in controle group, 50 nanomole, 100 nanomole, 10 micromole and 1 mictomole after 24 houre were 26/70, 38/54, 27/33, 31/34 and 29/05 respectively, and 50 nanomole had meaningful difference in comparison to controle group (P?0.05). After 48 h of incubation the results were 44/50, 59/37, 48/66, 46/26 and 37/16 respectively which 50 nanomole had meaningful difference in comparison to controle group (P?0.05). Our findings in this research show that Empagliflozin is an effective element in oocyte in vitro maturation and it could affect oocytes in order to achive MII phase dose depending, and it could be used as a suppliment in oocyte culture media. Key words: in vitro maturation, empagliflozin, oocyte, mouce

   In the tumor microenvironment, differences in cancer cells' access to nutrients and oxygen modify cellular metabolism. Hypoxic cancer cells turn to glycolytic metabolism to survive and proliferate, producing large amounts of lactate that must be tra  orted out of the cell. During a metabolic symbiosis, oxidative cancer cells import the excess lactate and use it as a preferred fuel instead of glucose. Lactate tra  ort is facilitated by monocarboxylate membrane tra  orters (MCTs) belonging to the solute carrier gene family-16, which is a proton-dependent process and plays a role in intracellular pH regulation. The export of lactate from the cell is mainly facilitated by MCT4, while MCT1 mediates its intracellular uptake. Overexpression of these tra  orters has been shown to be associated with a variety of malignancies, including breast, gastric, lymphoma, brain, lung, skin, and soft tissue cancers, and targeting them could be a potential treatment for some types of cancer. In this study, we used various virtual screening techniques including pharmacophore modeling, molecular docking and molecular dynamics simulation to identify effective and potential drug candidates against human MCT1. The atomic coordinates of the protein in outward-open conformation were downloaded from the protein data bank with the code 6LYY, and a library of chemical compounds including 12 million molecules purchasable from the ZINC database and 4683 FDA-approved drugs was created. After performing the preparation steps, molecular docking calculations were performed based on a consensus approach using AutoDock Vina, Molegro, and DOCK programs. Ligands with high binding energy were analyzed in successive steps, and their interaction with key residues of the protein active site was investigated. Finally, seven ligands that showed promising results were selected for the molecular dynamics simulation study. For each protein-ligand complex in the membrane bilayer, calculations of protein backbone RMSD, ligand RMSD, RMSF, and interaction analyses were performed. The results showed that Olmesartan, an angiotensin II receptor inhibitor, can have an inhibitory effect on human MCT1 with a strong and stable binding and pave the way to inhibit this tra  orter. Since this study is based solely on computational tools, further evaluation in experimental conditions is necessary to confirm its effectiveness.

Due to their favorable biocompatible properties, titanium and its alloys are used as popular raw materials for making all kinds of implants. Therefore, the efficiency of the implant is always being developed in order to better adapt to the biological tissue and increase its retention time in the place of cultivation, in different ways that lead to the creation of an oxide layer on the surface. The aim of this research is to investigate the biocompatibility of titanium in different morphologies obtained from anodizing in alkaline and acidic electrolytes.  

      In recent years and with the increase in the number of elderly people in different countries, the supply and demand for the use of titanium and its alloys in the manufacture of implants used in the human body such as hip joint prosthesis, joint replacement, knee replacement, fracture fixation and dental implants have increased.   has increased widely.   In medical applications, in addition to the usual properties of alloys, other factors such as topography and surface energy are also considered, which play an important role in the adhesion of bone cells to the implanted surface.   As a result, the surface of the material plays an important role in the body's response to the implantable material.   The purpose of this research is to investigate the effect of some variables of the sandblasting process, acid washing and heat treatment on the surface characteristics and cellular response of titanium.   In order to modify the surface of the titanium substrate, first the samples were sandblasted using alumina powder, then they were etched in a solution containing nitric acid and sulfuric acid for the necessary time.   After that, the samples were placed in the oven at temperatures of 300, 400, and 500 degrees Celsius for one hour. A group of samples were left without heat treatment.   In order to measure roughness, hydrophilicity, investigate surface morphology, investigate phase compounds, cytotoxicity and biocompatibility of substrates, various tests and equipment including roughness meter, water contact angle measurement system, XRD, cytotoxicity and SEM were used to investigate cellular morphology.   The results of the X-ray diffraction test showed that the dominant phase formed is the Ti6O phase.   Of course, a small amount of Ti2O3 was also formed.   The above groups cause better calcium deposition through reaction with body fluids.   And the results of the hydrophilicity test showed that the amount of wetting angle ?m decreased with increasing sandblast pressure and especially with heat treatment compared to the control samples.   However, in most of the samples, by increasing the temperature of heat treatment to 500 degrees Celsius, the contact angle has increased and the wettability has decreased.   Regarding the evaluation of cell viability, the produced levels did not show any signs of cytotoxicity.   In fact, the roughness of the surfaces obtained after sandblasting and acid etching were able to strengthen the attachment and proliferation of MG-63 cells on their surfaces.

  Carbonic anhydrase (CAs, EC 4. 2. 1. 1) is a family of zinc metalloenzymes that catalyzes vital reactions including the reversible conversion of carbon dioxide and water to bicarbonate and a proton. Carbonic anhydrase isozymes are involved in various physiological and pathological processes and are considered as important drug targets for the treatment of a wide range of disorders including glaucoma and various types of cancer. In this study, new sulfonamide derivatives resulting from the coupling reaction of sulfanilamide with benzene or its mono-, di-, tri- carboxylic acid compounds were chemically synthetized and their interaction with hCA II isozyme were investigated by various spectroscopic techniques. Kinetic results revealed that new sulfonamide derivatives inhibit the esterase activity of hCA II in a reversible competitive manner. As a result, among the studied compounds, compound 4 had the lowest Ki and IC50 values for hCA II isozyme. Also, fluorescence measurements showed that these compounds quench the intrinsic fluorescence of hCA II by a dynamic quenching mechanism. In addition, analysis of the thermodynamic parameters of the binding revealed that hydrogen bonds and van der Waals interactions play the major role in stabilization of the enzyme–drug complexes. Fluorescence analysis of the CAII-DNSA fluorescent complex in the presence of different concentrations of new sulfonamide derivatives showed the lowest dissociation constant (Kd) for the compound 4, indicating a higher affinity of this compound for the binding to the hCA II isozyme. Overall, the strengthening of the binding power and inhibitory activity of the studied sulfonamide derivatives for the hCA II isozyme, makes these derivatives of great interest for the design of novel hCA inhibitors.

  Carbonic anhydrases (EC 4.2.1.1) are zinc metalloenzymes that catalyze the reversible hydration of CO2 to HCO3? and proton. These enzymes have different distribution in different tissues and subcellular locations, and found in the archaea, eubacteria, animals and plants.These enzymes contributed in vital physiological processes associated with respiration and transfer CO2, secretion of electrolytes in tissues and lungs, pH adjustment, homeostasis, biosynthetic reactions (such as gluconeogenes and lipogenes) and calcification. Carbonic anhydrase inhibitors are a 20px;">Considering all the above data, it can be concluded that binding of 1-(4-chloro-benzenesulfonyl)-4-hydroxy-pyrrolidine-2-carboxylic acid to human carbonic anhydrase II caused changes   in the function as well as in the secondary and tertiary structure of the protein. Keywords: 1-(4-chloro-benzenesulfonyl)-4-hydroxy-pyrrolidine-2-carboxylic acid, Human Carbonic Anhydrase II, Inhibition, Thermodynamic Stability, Kinetic Stability, Fluorescence, Quenching