Rattus Norvegicus Research Articles

Potential application of a combined extract of Channa striata and calcium hydroxide for inhibiting lymphocytes and interleukin-1β cells in the asymptomatic irreversible pulpitis of Wistar rats (Rattus norvegicus).

This study aimed to evaluate the effectiveness of combining Channa striata extract with calcium hydroxide (Ca(OH)2) in reducing lymphocyte counts and interleukin (IL)-1β levels in inflamed pulp teeth. A laboratory experimental setup with a posttest control group (CG) design was employed. Thirty-two rat incisor teeth were divided into four groups: a positive CG (100% Ca(OH)2), treatment 1 (25% C. striata extract + 75% Ca(OH)2), treatment 2 (50% C. striata extract + 50% Ca(OH)2), and treatment 3 (75% C. striata extract + 25% Ca(OH)2). These test materials were applied to Class 1 cavities extending to the pulp roof, with samples collected on days 1, 3, 5, and 7. Data were analyzed using analysis of variance and post hoc least significant difference tests. In all the groups, the highest levels of lymphocytes and IL-1β were observed on day 3, followed by a decline on days 5 and 7. The combination of C. striata extract with Ca(OH)2 significantly reduced inflammatory markers, particularly lymphocyte and IL-1β levels. The extract of C. striata holds significant potential as an innovative therapeutic approach for managing inflamed dental pulp.

Protective Effect of Aloe vera (L.) on Diabetes-Induced Oxidative Stress Linked Spermiological Co-Morbidity in Human and Rat: An In-Vitro Analysis.

Diabetes linked reproductive complications are rising problems nowadays. The study focused on the protective efficacy of Aloe vera (L.) on sperm cell damage in an oxidative stress milieu encumbered by a chronic diabetes in human and streptozotocin treated Wistar rat (Rattus norvegicus). Spermatozoa from rat's epididymal washing, and human semen after 3-4days of abstinence of mating or masturbation were collected from control and diabetes groups. Spermatozoa of human and rat were incubated for 1 or 2h at 370C in an in-vitro medium separately and considered as normo-glycemic control and diabetes sub-groups. Dose of 1 or, 2 or, 4mg/ml of Aloe vera (L.) hydro-ethanolic (40:60) extract (AVHE) was given to diabetes samples, considered as sub-sub-group for assessing its protective effect on spermiological and oxidative stress parameters. The motility, viability, plasma membrane integrity, nuclear chromatin decondensation for DNA fragmentation, acrosome cap status, and antioxidative status of human and rat spermatozoa were decreased whereas spermatozoal apoptosis was elevated significantly (p < 0.05), noted by TUNEL assay in diabetes samples compared to the duration-matched control group. Exposure of AVHE to diabetes samples resulted significant rectification (p < 0.05) in the said parameters than the unexposed diabetes group. In control group, AVHE exposure has significant protective effect from spermiological deterioration compared to unexposed control group. Identification of major phytomolecules in AVHE was done by LC-MS study. Diabetes-induced oxidative stress-mediated spermatozoal injuries can be protected by AVHE extract, raise the possibility for potentiating sperm of human for increasing the success rate of in-vitro fertilization-blastocyst implantation.

Monitoring SARS-CoV-2 infection in urban and peri-urban wildlife species from Catalonia (Spain)

BackgroundHuman activities including deforestation, urbanization, and wildlife exploitation increase the risk of transmission of zoonotic diseases. Urban and peri-urban wildlife species often flourish in human-altered environments, with their survival and behavior heavily influenced by human-generated food and waste. In Catalonia, Spain, and other Mediterranean regions, species of rodents, including the house mouse (Mus musculus), black rat (Rattus rattus), Norway rat (Rattus norvegicus), as well as wild boar (Sus scrofa) are common in urban and peri-urban areas. These species host numerous infectious agents, including coronaviruses (CoVs), posing potential human health risks. During the coronavirus disease 2019 (COVID-19) pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved to infect previously non-susceptible species, with variants capable of infecting rodents, emphasizing their importance in surveillance studies.MethodsThe present study assessed SARS-CoV-2 presence and/or exposure in 232 rodents, 313 wild boar, and 37 Vietnamese Pot-bellied pigs in Catalonia during the pandemic period (2020–2023).ResultsAll the animals tested for acute SARS-CoV-2 infection (232 rodents and 29 wild boar) were negative. For SARS-CoV-2 exposure, 3 out of 313 (0.96%) wild boar tested positive by ELISA, while the remaining 32 rodents, 310 wild boar, and 37 Vietnamese Pot-bellied pigs were all negative. Cross-reactivity with other CoVs was predicted for ELISA-positive samples, as the 3 wild boar tested negative by the virus neutralization assay, considered as the gold standard technique.ConclusionsThe absence of SARS-CoV-2 exposure or acute infection in wild boar and rodent species supports their negligible role in viral spread or transmission during the COVID-19 pandemic in Catalonia. However, their proximity to humans and the ongoing genetic evolution of SARS-CoV-2 underline the need for continued monitoring. Surveillance of SARS-CoV-2 infection in animal species can contribute to design measures to control the emergence of new animal reservoirs or intermediate hosts that could facilitate viral spillover events.

The discovery of novel variants reveals the genetic diversity and potential origin of Seoul orthohantavirus.

Seoul orthohantavirus (SEOV) has been identified as one of the main causative agents of hemorrhagic fever with renal syndrome (HFRS) in China. The virus was found circulating in rodent populations in almost all provinces of the country, reflecting the wide distribution of HFRS. Here, using the direct immunofluorescence assay (DFA) and real-time quantitative reverse transcription PCR (qRT-PCR) approach, we performed screening in 1784 small mammals belonging to 14 species of three orders captured in the main areas of HFRS endemicity in Yunnan province (southwestern China) and identified 37 SEOV-positive rats (36 Rattus norvegicus and 1 Rattus tanezumi). A 3-year surveillance of HFRS epidemics and dynamics of rodent reservoir density and virus prevalence implied a potential correlation between them. The subsequent meta-transcriptomic sequencing and phylogenetic analyses revealed three SEOV variants, among which two are completely novel. The ancestral character state reconstruction (ACSR) analysis based on both novel variants and documented strains from 5 continents demonstrated that SEOV appeared to originate near the southwestern area (Yunnan-Kweichow Plateau) of China, then could spread to other regions and countries by their rodent carriers, resulting in a global distribution today. In summary, these data furthered the understanding regards genetic diversity and the potential origin for SEOV. However, the expanding endemic foci in the province suggest that the virus is spreading over a wider region and is much more diverse than previous depicted, which means that increased sampling is necessary.

Mulberry (Morus alba L.) leaf extract enhanced spermatozoa motility, viability, and plasma membrane integrity of rats (Rattus norvegicus) exposed to e-cigarette smoke

This study investigates the impact of mulberry leaf extract on the viability, plasma membrane integrity, and motility of spermatozoa from male white rats (Rattus norvegicus) exposed to e-cigarette smoke. A total of twenty-five male rats were divided into five groups: negative control (NC), positive control (PC), T1, T2, and T3. All groups, except for the NC group, were exposed to e-cigarette smoke. Rats in the T1, T2, and T3 groups received mulberry leaf extract in doses of 100, 200, and 400 mg/kg bw, respectively, while the NC and PC groups were given a placebo of 1% Na-CMC. Both the mulberry leaf extract and the placebo were administered daily, beginning three days prior to the start of e-cigarette smoke exposure, which lasted for 28 days. Results showed that spermatozoa motility, plasma membrane integrity, and viability in the experimental groups were significantly lower than those in the NC group (p &lt;0.05). Conversely, rats in the T1, T2, and T3 groups that received mulberry leaf extract demonstrated significantly greater spermatozoa viability, plasma membrane integrity, and motility compared to the PC group (p &lt;0.05). The T3 group exhibited the most pronounced improvements, with significantly enhanced spermatozoa viability, membrane integrity, and motility (p &lt;0.05) relative to the PC group. These results indicate that mulberry (Morus alba L.) leaf extract enhanced spermatozoa viability, plasma membrane integrity, and motility in white rats (Rattus norvegicus) subjected to e-cigarette smoke.

Effect of methanol extract of cloves (Syzigium aromaticum) on Protein Gene Product 9.5 in the testes of rats (Rattus norvegicus) with induced cryptorchidism

This study aimed to know the effect of cloves (Syzigium aromaticum) methanol extracts as an antioxidant on the germ cells of white rats (Rattus norvegicus) with induced cryptorchidism. The subjects of this study were 24 male white rats aged 21 days, who were divided into six groups. Rats were adapted for 5 days, after which cryptorchidism were induced. Cloves extract was given for 18 days and 36 days. On day-19 and day-37, rats were sacrificed and testicles were taken for Protein Gene Product (PGP) 9.5 detection by immunohistochemistry. These groups consisted of negative control group (given distilled water and sham surgery), positive control group (induction of cryptorchidism and given distilled water), and T treatment group (induction of cryptorchidism and given 70mg/kg bw cloves extract. Kruskal-Wallis test indicated a significant difference (p &lt;0.05). The differences between treatments were shown based on the outcome of the Mann-Whitney test. Cloves acted as an antioxidant for cryptorchid testicular germ cells. It could be concluded that administering methanol extract of clove flowers could ameliorate the expression of PGP 9.5 in the testicular germ cells of white rats in a model of unilateral cryptorchidism.

Widespread exposure to anticoagulant rodenticides among common urban mesopredators in Chicago

Anticoagulant rodenticides (ARs) are currently the most common method to control rats in cities, but these compounds also cause morbidity and mortality in non-target wildlife. Little attention has been focused on AR exposure among mesopredators despite their ecological role as scavengers and prey for larger carnivores, thus serving as an important bridge in the biomagnification of rodenticides in food webs. In this study, we sampled liver tissue from raccoons (Procyon lotor; n = 37), skunks (Mephitis mephitis; n = 15), and Virginia opossums (Didelphis virginiana; n = 45) euthanized by pest professionals and brown rats (Rattus norvegicus; n = 101) trapped in alleys in Chicago, USA to evaluate how often these species are exposed to ARs. We tested whether mesopredators had a higher prevalence of ARs and to more AR compounds compared to rats and calculated biomagnification factors (mean concentration in mesopredators/rats) as indicators of biomagnification. Of 93 sampled mesopredators, 100 % were exposed to at least one AR compound, mainly brodifacoum (≥80 %), and 79 % were exposed to multiple AR compounds. We also documented teal stomach contents consistent with the consumption of rat bait and altricial young tested positive to the same AR as their mother, suggesting mammary transfer. Of the 101 rats, 74 % tested positive to at least one AR compound and 32 % were exposed to multiple AR compounds. All mesopredator species had biomagnification factors exceeding 1.00 for brodifacoum (6.57–29.07) and bromadiolone (1.08–4.31). Our results suggest widespread exposure to ARs among urban mesopredators and biomagnification of ARs in mesopredators compared to rats. Policies that limit AR availability to non-target species, such as restricting the sale and use of ARs to licensed professionals in indoor settings, education on alternatives, and more emphasis on waste management may reduce health risks for urban wildlife and people in cities around the world.

Leptospira infection of rodents captured at the slaughterhouses and their risk to public health in Unguja island, Tanzania

Background: Leptospira infection is an invasion of animal or human body with the pathogenic spirochete bacteria of the genus Leptospira resulting to a disease called leptospirosis. This study aimed to investigate Leptospira infection and the carrier status of rodents caught near slaughterhouses at Unguja Island, Tanzania. Methods: This cross-sectional study was conducted from January to April 2022 at Unguja Island to determine the seroprevalence of Leptospira infection in rodents captured in and around the slaughterhouse’s compounds. A total of 302 sera samples from four slaughterhouses were tested for anti-leptospiral antibodies using microscopic agglutination test (MAT) with a panel of 5 Leptospira serovars: Pomona, Lora, Hebdomadis, Grippotyphosa and Sokoine; and were considered positive at MAT titer ≥1:20. Chi-square test and the Fisher exact test were used to assess the statistical association between variables at a p value of &lt; 0.05. Results: The overall seroprevalence of Leptospira infection in rodents was 10.6% (32/302). Individual rodent species had seroprevalence of 8.5% for Mus musculus, 0.0% for Mastomys natalensis, 20.8% for Rattus norvegicus, 9.3% for Rattus rattus and Cricetomys gambianus at 12.5%. However, the apparent seroprevalence in the individual slaughter facilities was 15.0% (15/100) Kinyasini, 10.4% (5/48) Mfenesini, 9.3% (5/54) Kisakasaka, and 7.0% (7/100) Muwanda. Conclusion: With over ten percent of rodents testing positive for Leptospira infection, it is crucial to implement rodent control measures to prevent the spread of the disease to those working in or around the slaughterhouses in Unguja Island.

Descripción de alteraciones histopatológicas en riñones de &lt;i&gt;Rattus norvegicus&lt;/i&gt; seropositivos a &lt;i&gt;Leptospira &lt;/i&gt;spp.

The aim of this study was to describe the most common histopathological findings observed by Hematoxylin-Eosin staining in kidneys of Rattus norvegicus naturally infected and seropositive to Leptospira spp using the Microscopic Agglutination Test (MAT) technique. In total, 165 rodents were captured from three locations in Antioquia (Turbo and Medellín). Kidney samples were taken from the seropositive rodents by MAT and Hematoxylin-Eosin staining was used to evaluate the microscopic lesions and Warthin- Starry to visualize the bacteria. The most frequent morphological diagnoses were chronic interstitial nephritis (45.0%), followed by vascular congestion (20.1%) and chronic interstitial pyelonephritis (10.6%). The pathological processes were classified 73.1% as moderate and 26.9% as mild. The agent was not observed with the Warthin starry stain.

Valacyclovir and Acyclovir Are Substrates of the Guanine Deaminase Cytosolic PSD-95 Interactor (Cypin).

Valacyclovir, enzymatically hydrolyzed in the body to acyclovir, is a guanine-based nucleoside analog commonly prescribed as an antiviral therapy. Previous reports suggest that guanosine analogs bind to guanine deaminase; however, it is unclear whether they act as inhibitors or substrates. Data from our laboratory suggest that inhibition of guanine deaminase by small molecules attenuates spinal cord injury-induced neuropathic pain. Here, we examine whether the guanosine analogs valacyclovir and acyclovir are deaminated by cypin (cytosolic PSD-95 interactor), the major guanine deaminase in the body, or if they act as cypin inhibitors. Using purified Rattus norvegicus cypin, we use NADH-coupled assay to confirm deamination of valacyclovir and determined Michaelis-Menten constants. Subsequently, we use tryptophan fluorescence quenching assay to calculate dissociation constants for valacyclovir and acyclovir and find that inclusion of the valine motif in valacyclovir increases affinity for cypin compared to acyclovir. To our knowledge, neither Km nor KD values for cypin has been previously reported for either compound. We use Amplex Red assay and demonstrate that both valacyclovir and acyclovir are cypin substrates and that their metabolites are further processed by xanthine oxidase and uricase. Using molecular dynamics simulations, we demonstrate that an alpha helix near the active site is displaced when valacyclovir binds to cypin. Furthermore, we used LC-MS-based assay to directly confirm deamination of valacyclovir by cypin. Taken together, our results demonstrate a novel role for cypin in deamination of valacyclovir and acyclovir and suggest that therapeutics based on purine structures may be inactivated by cypin, decreasing inhibitory efficacy.

Renal biomarkers of Rosemarinus officinalis L. on gentamicine induced acute kidney injury in adult male albino rats (Rattus norvegicus)

Renal biomarkers of Rosemarinus officinalis L. on gentamicine induced acute kidney injury in adult male albino rats (Rattus norvegicus)

Comparative morphology of the rhinarium and upper lip in sigmodontine rodents: Refined nomenclature, intertribal variation in a phylogenetic framework, and functional inferences.

Rodents have received substantial attention in the study of olfaction. However, the rhinarium, the naked part of the nose, which plays an important role in chemical, tactile, and thermal perception, has been relatively overlooked. This study presents a comprehensive analysis of the rhinarium morphology and spatially associated structures (i.e., upper lip, and philtrum) in sigmodontines, a diverse group within the Cricetidae rodents. The research covers 483 specimens representing 145 species, accounting for 74% of genera in the clade, including all 13 recognized tribes, three incertae sedis genera, and the murid representatives Mus musculus and Rattus norvegicus. The inconsistent use of terminology in describing rhinarium traits across the literature poses a challenge for comparative analyzes. To address this issue, a standardized terminology was proposed to characterize the rhinarium. A paired complex protuberance typically with epidermal ridges (i.e., rhinoglyphics), termed here the tubercle of Hill, was identified as a distinctive feature in muroid rhinaria. Comparative assessments among tribes revealed unique sets of features defining each major clade, encompassing variations in hairiness, dorsum nasi complexity, size and positioning of the tubercle of Hill, and other key attributes. Two primary rhinarium configurations were discerned: one shared by Oryzomyalia and Sigmodontini and another specific to Ichthyomyini. The former groups display a ventrally positioned rhinarium prominently featuring the tubercle of Hill and sculptured areola circularis. In contrast, Ichthyomyini exhibit a frontally directed rhinarium characterized by an enlarged dorsum nasi fused to the tubercle of Hill, resulting in a distinctive "cherry" appearance. Convergent rhinarium structures observed in fossorial species, characterized by well-developed plica alaris and hair fringes, are presumed to mitigate potential damage during digging. Conversely, semiaquatic carnivorous sigmodontines showcase an integrated apical structure in their rhinarium, facilitating enhanced somatosensory capabilities crucial for predation activities during diving expeditions.

Intraspecific Variation of Brown Rat Rattus norvegicus in Russia by D-Loop mtDNA Data.

For the first time in Russia, the intraspecific structure of the brown rat Rattus norvegicus was studied using the mitochondrial control region (D-loop) as a molecular marker. The mtDNA sequence was determined in brown rats from eight regions of European and Asian Russia. Three rat clades were identified, including one in European Russia and two in Asian Russia. The synanthropic subspecies R. n. norvegicus was found to have two, European and Asian, lineages. The European lineage included haplotypes from central and southern regions of Russia, and the Asian lineage included haplotypes from Eastern Siberia and the Russian Far East. The exoanthropic subspecies R. n. caraco from the Russian Far East formed a separate genetic lineage.

Determinants of pegivirus persistence, cross-species infection, and adaptation in the laboratory mouse.

Viruses capable of causing persistent infection have developed sophisticated mechanisms for evading host immunity, and understanding these processes can reveal novel features of the host immune system. One such virus, human pegivirus (HPgV), infects ~15% of the global human population, but little is known about its biology beyond the fact that it does not cause overt disease. We passaged a pegivirus isolate of feral brown rats (RPgV) in immunodeficient laboratory mice to develop a mouse-adapted virus (maPgV) that established persistent high-titer infection in a majority of wild-type laboratory mice. maRPgV viremia was detected in the blood of mice for >300 days without apparent disease, closely recapitulating the hallmarks of HPgV infection in humans. We found a pro-viral role for type-I interferon in chronic infection; a lack of PD-1-mediated tolerance to PgV infection; and multiple mechanisms by which PgV immunity can be achieved by an immunocompetent host. These data indicate that the PgV immune evasion strategy has aspects that are both common and unique among persistent viral infections. The creation of maPgV represents the first PgV infection model in wild-type mice, thus opening the entire toolkit of the mouse host to enable further investigation of this persistent RNA virus infections.

Histomorphometric analysis of the soleus muscle in different phases of ischemic stroke in an animal model

Objective: To analyze the muscle mass and cross-sectional area of the muscular fiber of the hemiparetic soleus in an animal model, in order to identify the muscular adaptations that occur in ischemic stroke. Method: Twelve Rattus norvegicus were divided into 2 groups: stroke group (n=6) and control group (n=6). Each group was subdivided into two subgroups, with evaluations at 7 days (CG7 and SG7) and 21 days (CG21 and SG21) after the accident. Their soleus muscles were removed for muscle mass analysis and cross-sectional area of the muscular fibers (CSAMF) measurement. The adopted statistical significance was 5%. Result: Significant differences in the muscle mass were observed between CG7 (0.120 ± 0.005 g) vs. SG7 (0.100 ± 0.004 g; p=0.035), and between CG21 (0.130 ± 0.010 g) vs. SG21 (0.078 ± 0.006; p=0.012). Significant differences in the relative muscle mass were observed between CG7 (0.044 ± 0.002 g) vs SG7 (0.039 ± 0.003; p=0.025), and CG21 (0.044 ± 0.003) vs. SG21 (0.028 ± 0.002; p=0.011). The CSAMF showed significant differences between CG7 (2,322 μm2 [2312-2453]) vs. SG7 (2,056 μm2 [2,022-2,135]; p=0.012), and CG21 (2,667 μm2 [2,692-2,845]) vs. SG21 (2,050 μm2 [2,034-2,161]; p=0.006). Conclusion: In this study in animal models of ischemic stroke, there was a significant loss of muscle mass, and this loss was accentuated in the longer term of the injury, highlighting the importance of future research on types of muscle fibers and applicability in human patients.

Improvement of Liver Function (AST and ALT) and Liver Tissue Catalase levels of Wistar rats induced with Alloxan by consuming Catfish oil extract

Background: Background: Type 2 Diabetes Mellitus (T2DM) is characterized by disrupted glucose metabolism, leading to hyperglycemia and insulin resistance, often associated with Secondary Hypertension (SH). Over 80% of SH patients exhibit glucose intolerance, with nearly 30% developing T2DM. There is a strong interaction between T2DM and NAFLD, representing a complex two-way relationship that influences the prognosis of the two diseases. Catfish oil extract boasts unsaturated fatty acids, including DHA, EPA, omega-3, vitamins A, B6, B12, D, and amino acids. Objective: This study aims to assess the impact of Pangasius sp. (catfish) oil extract administration on serum AST and ALT levels, as well as liver tissue MDA and CAT levels in alloxan-induced Wistar rats (Rattus norvegicus). Materials and Methods: Employing a pure experimental approach with a post-test-only control group design, three groups of 9 white male rats (Rattus norvegicus), along with one extra male rat, were included.K1 served as the negative control group (Wistar rats not subjected to any treatment). K2 acted as the positive control group (Wistar rats subjected to alloxan-induced diabetes at 150mg/kg BW). K3 represented the treatment group (diabetic model rats treated with catfish oil extract at 73mg/kg BW). Serum AST and ALT levels, as well as MDA and CAT levels in liver tissue, were measured at the study's conclusion. Results: The highest mean MDA levels in white rat liver tissue were K2 (3034.00 + 525.25 nmol/g), and the lowest was K3(2909.33+351.01nmol/g); the mean CAT liver tissue levels in rats the highest was K1 (1063.42+133.36U/mg), and the lowest was K3(894.78+132.93U/mg), the highest mean serum ALT levels of white rats was K2(230.34+63,58 U/L), and the lowest was K1(151.54+23.12 U/L) and the highest mean serum AST level in rats was K2(448.79+618.90U/L), and the lowest was K1(61.01+14.70U/L). Conclusion: Giving catfish oil supplementation can repair the damage in liver tissue, as evidenced by reductions in MDA levels and serum ALT and AST levels in diabetic model rats within the treatment group. Alloxan induction did not affect liver tissue CAT levels, as evidenced by a consistent decrease in liver tissue CAT levels in both the positive control and treatment groups.

The Effects of Olive Oil (Olea Europaea L.) on Cathallase Enzyme Levels in White Rats (Rattus Norvegicus) Wistar Strain of Obese Male

Obesity is a condition of the body resulting from excessive fat accumulation which leads to health problems. The increase in fat metabolism affects increased production of free radicals in the circulation and in adipocyte cells. Free radicals that increase in the body are not in line with antioxidant enzymes, causing a condition called oxidative stress. The body's defense mechanism against free radicals is the synthesis of antioxidants. When there is a decrease in the activity of endogenous antioxidants such as the catalase enzyme, it provides a strong indication of oxidative stress. The presence of polyphenols and monounsaturated fatty acids in olive oil is useful for preventing chronic damage that causes oxidative stress. The catalase enzyme can be used as a parameter for an uncontrolled increase in ROS (Reactive Oxygen Species) or disruption of the function of the antioxidant defense system. To determine changes in levels of the catalase enzyme in an obese male Wistar strain white rat (Rattus norvegicus) animal model that was given olive oil. This research used a true experimental laboratory with a pre- post test design. The results of the study were significant changes in catalase enzyme levels in the olive oil intervention group (p-value 0.003&lt;0.05) on day 14 and day 28 with (p-value 0.002&lt;0.05 and 0.005&lt;0.05). In the group given olive oil, the effect on the level of catalase enzyme was most significant on day 28 (p-value 0.002&lt;0.05).

Carbon fiber felt scaffold from Brazilian textile PANfiber for regeneration of critical size bone defects in rats: A histomorphometric and microCT study.

The objective of the present study was to evaluate the carbon fiber obtained from textile PAN fiber, in its different forms, as a potential scaffolds synthetic bone. Thirty-four adult rats were used (Rattus norvegicus, albinus variation), two critical sized bone defects were made that were 5 mm in diameter. Twenty-four animals were randomly divided into four groups: control (C)-bone defect + blood clot, non-activated carbon fiber felt (NACFF)-bone defect + NACFF, activated carbon fiber felt (ACFF)-bone defect + ACFF, and silver activated carbon fiber felt (Ag-ACFF)-bone defect + Ag-ACFF, and was observed by 15 and 60 days for histomorphometric, three-dimensional computerized microtomography (microCT) and mineral apposition analysis. On histomorphometric and microCT analyses, NACFF were associated with higher proportion of neoformed bone and maintenance of bone structure. On fluorochrome bone label, there was no differences between the groups. NACFF has shown to be a promising synthetic material as a scaffold for bone regeneration.

Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf-2/Keap-1, Inflammatory, Steroidogenic, and Histological Profile.

Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ-induced testicular toxicity in rats. Forty-eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap-1 while downregulating the expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD), 17-beta hydroxysteroid dehydrogenase (17β-HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-1beta (IL-1β), and cyclooxygenase-2 (COX-2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate-specific proteases-3 (Caspase-3) and Bcl-2-associated X-protein (Bax) while downregulating the expressions of B-cell lymphoma-2 (Bcl-2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti-inflammatory, and androgenic potential.

SGLT2 inhibition improves PI3Kα inhibitor–induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials

PurposeAlpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+ /HER2− advanced breast cancer (ABC) (SOLAR-1). Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. We report data from preclinical models and two clinical trials (SOLAR-1 and BYLieve) on Sodium glucose cotransporter 2 inhibitor (SGLT2i) use to improve PI3Kα inhibitor–associated hyperglycemia.MethodsHealthy Brown Norway (BN), mild diabetic Zucker diabetic fatty (ZDF), and Rat1-myr-p110α/HBRX3077 tumor–bearing nude rats treated with alpelisib were analyzed for glucose and insulin control with metformin and dapagliflozin (SGLT2i) and alpelisib efficacy. Hyperglycemia adverse events (AEs) were compared between patients receiving SGLT2i with alpelisib (n = 19) and a propensity score–matched cohort not receiving SGLT2i (n = 74) in both trials.ResultsDapagliflozin and metformin in BN and ZDF rats treated with alpelisib normalized blood glucose and reduced insulin levels. No signs of ketosis or drug-drug interaction were observed when metformin and dapagliflozin was administered with alpelisib. Alpelisib antitumor efficacy was maintained when used with dapagliflozin in tumor-bearing rats. Compared with a matched set of patients without SGLT2i, patients receiving SGLT2i had 4.9 and 6.4 times lower rates of grade ≥ 3 hyperglycemia AEs and hyperglycemia AEs resulting in alpelisib dose adjustments, interruptions, or withdrawals, respectively, and a relative reduction in risk of experiencing these AEs (70.6% and 35.7%).ConclusionThese data suggest adding an SGLT2i can effectively manage hyperglycemia, resulting in fewer alpelisib dose modifications and discontinuations in patients with PIK3CA-mutated HR+ /HER2− ABC (SOLAR-1: NCT02437318; BYLieve: NCT03056755).