Investigation into effects of tocilizumab and epoetin beta in rats with experimental sciatic nerve injury model.

OBJECTIVE: To investigate the effects of tocilizumab (TCZ), epoetin beta (EPO), and their combination on nerve regeneration in a sciatic nerve injury model. MATERIALS AND METHOD: Male Sprague-Dawley rats were divided into (-) negative control, sham, TCZ, EPO ((+) positive control), and TCZ+EPO groups. The TCZ group received TCZ (8 mg/kg intraperitoneal) immediately after surgery. On day 14th, the EPO group received EPO (5000 IU/kg, intraperitoneal); the TCZ+EPO group received TCZ (8 mg/kg, intraperitoneal), EPO (5000 IU/kg, intraperitoneal), and TCZ (8 mg/kg, intraperitoneal) post-surgery. Motor and sensory functions were assessed pre and post-surgery. Lipid peroxidation and oxidative stress parameters were evaluated biochemically in the serum, and sciatic nerve tissue was evaluated histopathologically using haematoxylin-Eosin and Masson trichrome staining. CONCLUSIONS: TCZ and EPO decreased nerve injury effects by increasing motor and sensory conduction velocities of the sciatic nerve. Biochemically, TCZ and EPO significantly increased Superoxide Dismutase, Catalase, and Glutathione peroxidase 4 levels while decreasing Lipid Peroxidation levels (p=0.001). Histopathologically, neuronal degeneration following nerve injury was decreased in the groups receiving TCZ and EPO (p=0.001). EPO and TCZ attenuate the adverse effects of nerve injury. However, the TCZ+EPO treatment favoured biochemical activities over tissue and functional activities. This has been confirmed functionally, biochemically, and histopathologically.

Fullerene C60 protects against 7,12-dimethylbenz [a] anthracene (DMBA) induced-pancreatic damage via NF-κB and Nrf-2/HO-1 axis in rats.

The objective of this investigation was to investigate the protective effects of fullerene C60 nanoparticle against pancreatic damage experimentally induced by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Fullerene C60 nanoparticle was administered to rats 5 times a week by oral gavage (o.g) at 1.7 mg/kg bw 7 days after DMBA administration. 60 Wistar albino female rats divided to four groups; Groups: (1) Control group: Fed with standard diet; (2) Fullerene C60 group: Fullerene C60 (1.7 mg/kg bw); (3) DMBA group: DMBA (45 mg/kg bw); (4) Fullerene C60 + DMBA group: Fullerene C60 (1.7 mg/kg bw) and DMBA (45 mg/kg bw). Lipid peroxidation malondialdehyde (MDA), catalase activity (CAT) and glutathione (GSH) levels in pancreatic tissue were determined by spectrophotometer. Protein expression levels of p53, HO-1, p38-α (MAPK), Nrf-2, NF-κB and COX-2 in pancreatic tissue were determined by western blotting technique. In our findings, compared to the group given DMBA, MDA levels and p38-α, NF-κB and COX-2 levels decreased, CAT activity, GSH level, total protein density and p53, HO-1, Nrf-2 levels in the groups given fullerene C60 nanoparticle an increase in expression levels was observed. Our results showed that fullerene C60 nanoparticle may be more beneficial in preventing pancreatic damage.

Lutein/Zeaxanthin Isomers and Quercetagetin Combination Safeguards the Retina from Photo-Oxidative Damage by Modulating Neuroplasticity Markers and the Nrf2 Pathway.

Exposure to light-emitting diode (LED) light is a primary cause of retinal damage, resulting in vision loss. Several plant-derived substances, such as lutein and quercetagetin (QCG), show promise in supporting eye health. In this study, the impact of lutein/zeaxanthin (L/Z, Lutemax 2020) and QCG were evaluated individually and together in a rat model of LED-induced retinal damage. A total of 63 Wistar rats were allocated into nine groups (n = 7). For 28 days, the rats received L/Z (10 or 20 mg/kg BW), quercetin (QC, 20 mg/kg BW), QCG (10 or 20 mg/kg BW), or a mixture of different lutein and QCG dosages, after which they were exposed to LED light for 48 h. LED exposure led to a spike in serum malondialdehyde (MDA) and inflammatory cytokines, as well as an increase in retinal NF-κB, ICAM, GFAP, and MCP-1 levels (p < 0.0001 for all). It also reduced serum antioxidant enzyme activities and retinal Nrf2, HO-1, GAP43, NCAM, and outer nuclear layer (ONL) thickness (p < 0.0001 for all). However, administering L/Z and QCG, particularly a 1:1 combination of L/Z and QCG at 20 mg/kg, effectively reversed these changes. The treatment suppressed NF-κB, ICAM, GFAP, and MCP-1 while enhancing Nrf2, HO-1, GAP43, and NCAM and preventing ONL thickness reduction in LED-induced retinal damage rats. In conclusion, while LED light exposure caused retinal damage, treatment with L/Z, QC, and QCG, particularly a combined L/Z and QCG regimen, exhibited protective effects on the retina. This is possibly due to the modulation of neuroplasticity markers and nuclear transcription factors in the rats' retinal cells.

Garlic Exosomes Promote Hair Growth Through the Wnt/ß-catenin Pathway and Growth Factors.

Background Exosomes are membrane-derived nanovesicles produced by cells and play an important role in intercellular communication. Objectives This study aimed to investigate the effects of garlic exosome (GE) on hair growth. Methods Forty-two Sprague-Dawley/Wistar albino rats were randomly divided into six groups: non-shaved control, shaved control, topical control, GE 2 mg, GE 4 mg, and topical GE. At the end of the experiment, the number of hair follicles, follicle diameter, and subcutaneous tissue thicknesses were measured histopathologically. The Wnt-1, ß-catenin, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and collagen I levels were measured by the Western Blot method. Results The anagen follicle counts of the GE 2 mg, 4 mg, and topical GE groups were 66.57±15.49, 105.71±25.06, and 55.29±6.72, and were significantly higher than the control groups (p<0.01, p<0.001 and p<0.05, respectively). The follicle diameter of the GE 4 mg group was higher than the others (p<0.05). The Wnt-1, PDGF, VEGF, TGF-ß1, and collagen I levels of all GE groups, and the ß-catenin levels of the GE 4 mg and topical GE groups were significantly higher than the control groups (p<0.05). Conclusion GE induces hair growth in rats via the Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways.

Fullerene C60 reduces acute lung injury by suppressing oxidative stress-mediated DMBA-induced apoptosis and autophagy by regulation of cytochrome-C/caspase-3/beclin-1/IL-1α/HO-1/p53 signaling pathways in rats.

The objective of this study was to evaluate the effect of fullerene C60 nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tissue damage in rats. 60 Wistar albino (8 weeks old) female rats were assigned into four groups: Control Group (C), Fullerene C60, DMBA, and Fullerene C60+DMBA. The rats in the DMBA and Fullerene C60+DMBA groups were administered DMBA (45 mg/kg bw, oral gavage). The rats in Fullerene C60, and Fullerene C60+DMBA groups were administered with Fullerene C60 (1.7 mg/kg bw, oral gavage). Expression levels of cytochrome-C, caspase-3, beclin-1, IL-1α, HO-1 and p53 proteins in lung tissue were determined by western blotting, lipid peroxidation malondialdehyde (MDA) analyzes, glutathione (GSH), glutathione peroxidase (GSH-Px), catalase activity (CAT) and total protein levels were determined by spectrophotometer. In addition, lung tissues were evaluated by histopathologically. Fullerene C60 reduced the increasing of MDA and IL-1α protein expression levels and attenuated histopathological changes in lung. Moreover, fullerene C60 enhanced the protein expression of cytochrome-C, caspase-3, beclin-1, HO-1, and p53, which were decreased in the DMBA group. Fullerene C60 has strong biological activity that it might be an effective approach for lung damage.

How can we use positron emission tomography/computed tomography more accurately for characterization of asbestos-related pleural thickening?

Introduction: There is no consensus about the standardized uptake value maximum (SUVmax) cut-off value to characterize pleural thickening worldwide. Sometimes, this causes unnecessary invasive diagnostic procedures. Our first aim is to determine a cut-off value for SUVmax. Secondly, we try to answer the following question: If we use this cut-off value together with morphological parameters, can we differentiate benign thickening from malignant pleural mesothelioma (MPM) more accurately? Material and methods: Thirty-seven patients who underwent 2-deoxy-2-fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) before pleural biopsy were included the study. All of patients had histopathologically proven primary pleural disease. Their [18F]FDG-PET/CT imaging reports were re-assessed. If a patient's SUVmax or size of the thickening was not mentioned in the report, we calculated it with their [18F]FDG-PET/CT. Results: Age, pleural effusion, size, and SUVmax were found to have a relationship with MPM. We found the size > 14 mm, and SUVmax > 4.0 as cut-off values for MPM. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for size > 14 mm were found to be 86.4%, 85.2%, 82.6%, 88.5%, respectively. For SUVmax > 4.0, sensitivity, specificity, PPV, NPV were 90.9%, 87.0%, 85.1%, 92.2%, respectively. Conclusions: If a patient has SUVmax > 4.0 and/or size > 14 mm, the risk of MPM is high. These patients should undergo biopsy. If a patient's SUVmax < 4.0, size < 14 mm and does not have pleural effusion, he/she has low risk for MPM. These patients can undergo the follow-up. If a patient's SUVmax < 4, size < 14, and has pleural effusion the MPM risk is approximately 4%. These patients can undergo biopsy/cytology/follow-up. Novel studies are needed for these patients.

Royal jelly protects brain tissue against fluoride-induced damage by activating Bcl-2/NF-κB/caspase-3/caspase-6/Bax and Erk signaling pathways in rats.

This study is aimed at determining whether royal jelly (RJ) which has a powerful antioxidant property prevents fluoride-induced brain tissue damage and exploring whether Bcl-2/NF-κB/ and caspase-3/caspase-6/Bax/Erk pathways play a critical role in the neuroprotective effect of RJ. Wistar albino rats were chosen for the study, and they were randomly distributed into six groups: (i) control; (ii) royal jelly; (iii) fluoride-50; (iv) fluoride-100; (v) fluoride-50 + royal jelly; (vi) fluoride-100 + royal jelly. We established fluoride-induced brain tissue damage with 8-week-old male Wistar albino rats by administration of fluoride exposure (either 50 mg/kg or 100 mg/kg bw) through drinking water for 8 weeks. Then, the study duration is for 56 days where the rats were treated with or without RJ (100 mg/kg bw) through oral gavage. The effects of RJ on glutathione (GSH), catalase activity (CAT), and malondialdehyde (MDA) levels were determined via spectrophotometer. Western blot analysis was performed to investigate the effects of royal jelly on the protein expression levels of Bax, caspase-3, caspase-6, Bcl-2, NF-κB, COX-2, and Erk. It was also studied the effects of RJ on histopathological alterations in fluoride-induced damage to the rat brain. As a result, the Bcl-2, NF-κB, and COX-2 protein expression levels were increased in the fluoride-treated (50 and 100 mg/kg) groups but they were decreased significantly by RJ treatment in the brain tissue. Additionally, the protein expression of caspase-3, caspase-6, Bax, and Erk were decreased in fluoride-treated groups and they were significantly increased by RJ treatment compared to the un-treated rats. Our results suggested that RJ prevented fluoride-induced brain tissue damage through anti-antioxidant activities.

Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats.

The present study aimed to investigate the therapeutic effect of fullerene C60 nanoparticle against heart tissue damage caused by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Female Wistar albino rats, 8 weeks old (n = 60) weighing around (150 ± 10 g) were used for the study. These rats were divided into 4 groups and each group included 15 rats. Groups: (i) Control Group: Fed with standard diet; (ii) C60 Group: C60 (1.7 mg/kg bw, oral gavage); (iii) DMBA Group: DMBA (45 mg/kg bw, oral gavage); (iv) C60 and DMBA Group: C60 (1.7 mg/kg bw, oral gavage) and DMBA (45 mg/kg bw, oral gavage) group. Malondialdehyde (MDA) analysis, catalase activity (CAT), and glutathione (GSH) in heart tissue were determined by spectrophotometer. In addition, heart tissue DNA damage was investigated. Caspase-3, p53, HO-1, COX-2, and TNF-α protein expression levels in heart tissue were determined by western blotting. As a result, Caspase-3, p53, HO-1 protein expression, GSH levels and CAT activity increased, COX-2, TNF-α protein expression, and MDA levels were significantly decreased in the C60 + DMBA group compared to the DMBA group. Therefore, the fullerene C60 nanoparticle may be a promising and effective therapy for the treatment of heart diseases associated with inflammation.

Effects of a Combination of Arginine Silicate Inositol Complex and a Novel Form of Biotin on Hair and Nail Growth in a Rodent Model.

The purpose of this study was to examine the effects of a combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on hair and nail growth in an animal model. Twenty-eight female Sprague-Dawley rats (8 weeks old) were randomized into one of the following groups: (i) group (control), shaved; (ii) group (ASI), shaved + ASI (4.14 mg/rat/day); (iii) group (ASI + MgB I), shaved + ASI (4.14 mg/rat/day) + MgB (48.7 µg/rat/day); and (iv) group (ASI + MgB II), shaved + ASI (4.14 mg/rat/day) + MgB (325 µg/rat/day). On day 42, compared with the control group, while hair density (p < 0.05, p < 0.01, and p < 0.0001, respectively) and anagen ratio (p < 0.01, p < 0.01, and p < 0.001) increased in the ASI, ASI + MgB I, and ASI + MgB II groups, telogen ratio decreased (p < 0.01, p < 0.01, and p < 0.001, respectively). In the molecular analysis, VEGF, HGF, and KGF-2 increased in the ASI (p < 0.01, p < 0.01, and p < 0.05, respectively), ASI + MgB I (p < 0.0001 for all), and ASI + MgB II (p < 0.0001 for all) groups when compared to the control group. FGF-2 (p < 0.01) and IGF-1 (p < 0.001) were found to be increased in the ASI + MgB I and ASI + MgB II groups. SIRT-1 and ß-catenin increased in the ASI (p < 0.05 and p < 0.01), ASI + MgB I (p < 0.001 for both), and ASI + MgB II (p < 0.0001 for both) groups. Wnt-1 increased in the ASI + MgB I (p < 0.001) and ASI + MgB II (p < 0.0001) groups. In conclusion, the combination of ASI and MgB could promote hair growth by regulating IGF-1, FGF, KGF, HGF, VEGF, SIRT-1, Wnt, and ß-catenin signal pathways. It was also established that ASI did not affect nail growth, whereas the MgB combination was effective using a higher dose of biotin.

Royal jelly arranges apoptotic and oxidative stress pathways and reduces damage to liver tissues of rats by down-regulation of Bcl-2, GSK3 and NF-κB and up-regulation of caspase and Nrf-2 protein signalling pathways.

IntroductionRoyal jelly (RJ) from the honey bee, Apis mellifera, is a traditional product that is widely used as a food supplement to support the medical treatment of various diseases.Material and methodsOur study continued for 8 weeks. 42 Wistar albino (8 weeks old) male rats were used in the study. The study included 6 groups; Group 1: Control group (fed with standard diet), Group 2: RJ (100 mg/kg, bw), Group 3: F-50 (50 mg/kg, bw), group 4: F-100 (100 mg/kg, bw) group 5: F-50 (50 mg/kg, bw) + RJ (100 mg/kg, bw) Group 6: F-100 (100 mg/kg, bw) + RJ (100 mg/kg, bw). Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities in liver tissue were determined by spectrophotometer. Liver tissue samples were examined histopathologically and various protein levels were determined by Western blotting technique.ResultsRJ caused a significant decrease in MDA level, Bcl-2, GSK3 and NF-κB protein expression levels, whereas induced a significant increase in GSH level, CAT activities and Bax, BDNF, caspase-6, caspase-3, Nrf-2 protein expression levels.ConclusionOur findings suggest RJ to be used as a hepatoprotective agent in the clinic to modulate the toxic effects of fluoride and other chemicals in the future.

A new approach on the regulation of NF-κB and Bax protein signaling pathway activation by royal jelly in fluoride-induced pancreas damage in rats.

Forty-two healthy adult male rats (Wistar albino, n = 42, 8 weeks old, starting weights 200-250 g) employed in this study were subdivided into six groups randomly with seven rats per group as follows: (i) Control group: received standard diet; (ii) RJ group: received standard diet supplemented with royal jelly; (iii) F50 group: received standard diet supplemented with fluoride (50 mg/kg BW); (iv) F100 group: received standard diet supplemented with fluoride (100 mg/kg BW); (v) F50 +RJ group: received standard diet supplemented with fluoride (50 mg/kg BW) and royal jelly; (iv) F100 +RJ group: received standard diet supplemented with fluoride (100 mg/kg BW) and royal jelly. The study continued for a total of eight weeks. Western blot analysis was conducted to determine the post-translational expression levels of NF-κB, Bax, Bcl-2, TNF-α, Caspase-3 and Caspase-6 proteins in pancreas tissue. The pancreatic tissue was subjected to histopathological evaluation. Furthermore, MDA, GSH and CAT activities were examined by spectrophotometric analyzes. Our findings demonstrate that, compared to the control and RJ groups, Bcl-2 protein expression was augmented and, conversely, Caspase-6, Caspase-3 and Bax protein levels were decreased upon fluoride treatment. A statistically significant increase in TNF-α and NF-κB protein expressions was observed in the groups with fluoride-induced damage compared to the control and RJ groups. The MDA levels were increased in all fluoride-treated rats compared to those in the control and RJ groups, whereas the CAT and GSH activities were reduced in all rats with fluoride- induced damage. Although there was not a great difference between the groups regarding histopathological findings, there was a tendency to decrease in the rate of damage upon royal jelly treatment.

Evaluation of the potential of Rejuveinix plus dexamethasone against sepsis.

Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.

Protective effects of caffeic acid phenethyl ester (CAPE) and thymoquinone against cigarette smoke in experimental bone fracture healing.

This study investigated the protective characteristics of caffeic acid phenethyl ester (CAPE) and thymoquinone (TMQ) against the effects of cigarette smoke in recovery from bone fractures. Sixty Wistar albino rats were divided into six groups (n = 10). The rats' femur bones were fractured and then fixed with microplates and microscrews. In the CAPE group, CAPE was given by intraperitoneal injection for 30 days at a dose of 10 µmol/kg once a day. In the TMQ group, TMQ was given orogastrically for 30 days at a dose of 10 mg/kg once a day. In the cigarette groups, CAPE was given by intraperitoneal injection for 30 days at a dose of 10 µmol/kg once a day (CAPE-CG), TMQ was given orogastrically for 30 days at a dose of 10 mg/kg once a day (TMQ-CG), and controls were exposed to cigarette smoke three times a day for 8 min each time for 30 days. The controls received no postoperative treatment. The rats were sacrificed on the 30th day following surgery. According to the histopathological and immunohistochemical results, cigarette smoke had a negative impact on bone healing. TMQ and CAPE increased bone formation and reduced bone destruction. Therefore, TMQ and CAPE were found to be partially protective against the adverse effects of smoking on bone tissue.

In Vivo Evaluation of the Effects of B-Doped Strontium Apatite Nanoparticles Produced by Hydrothermal Method on Bone Repair.

In the present study, the structural, morphological, and in vivo biocompatibility of un-doped and boron (B)-doped strontium apatite (SrAp) nanoparticles were investigated. Biomaterials were fabricated using the hydrothermal process. The structural and morphological characterizations of the fabricated nanoparticles were performed by XRD, FT-IR, FE-SEM, and EDX. Their biocompatibility was investigated by placing them in defects in rat tibiae in vivo. The un-doped and B-doped SrAp nanoparticles were successfully fabricated. The produced nanoparticles were in the shape of nano-rods, and the dimensions of the nano-rods decreased as the B ratio increased. It was observed that the structural and morphological properties of strontium apatite nanoparticles were affected by the contribution of B. A stoichiometric Sr/P ratio of 1.67 was reached in the 5% B-doped sample (1.68). The average crystallite sizes were 34.94 nm, 39.70 nm, 44.93 nm, and 48.23 nm in un-doped, 1% B-doped, 5% B-doped, and 10% B-doped samples, respectively. The results of the in vivo experiment revealed that the new bone formation and osteoblast density were higher in the groups with SrAp nanoparticles doped with different concentrations of B than in the control group, in which the open defects were untreated. It was observed that this biocompatibility and the new bone formation were especially elevated in the B groups, which added high levels of strontium were added. The osteoblast density was higher in the group in which the strontium element was placed in the opened bone defect compared with the control group. However, although new bone formation was slightly higher in the strontium group than in the control group, the difference was not statistically significant. Furthermore, the strontium group had the highest amount of fibrotic tissue formation. The produced nanoparticles can be used in dental and orthopedic applications as biomaterials.

Protective effect of royal jelly on fluoride-induced nephrotoxicity in rats via the some protein biomarkers signalling pathways: a new approach for kidney damage.

INTRODUCTION: Protective effect of royal jelly (RJ) on fluoride-induced nephrotoxicity was investigated in this study. METHODS: 42 healthy male Wistar rats (n = 42, 8 weeks of age) were divided equally into 6 groups with 7 rats in each; (1) Group-1: Controls fed with standard diet; (2) Group-2: RJ [100 mg/kg] bw (body weight), by oral gavage; (3) Group-3: Fluoride [50 mg/kg] bw, in drinking water; (4) Group-4: Fluoride [100 mg/kg] bw, in drinking water; (5) Group-5: RJ [100 mg/kg] bw, by oral gavage + Fluoride [50 mg/kg] bw, in drinking water; (6) Group-6: RJ [100 mg/kg] bw, by oral gavage + Fluoride [100 mg/kg] bw, in drinking water. After 8 weeks, all rats were decapitated and their kidney tissues were removed for further analysis. The protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, VEGF, GSK-3, BDNF, COX-2 and TNF-α proteins in kidney tissue were analysed by western blotting technique. RESULTS: RJ increased Bcl-2, COX-2, GSK-3, TNF-α and VEGF protein levels and a decreased caspase-3, caspase -6, caspase-9, Bax and BDNF protein levels in fluoride-treated rats. CONCLUSION: RJ application may have a promising therapeutical potential in the treatment of many diseases in the future by reducing kidney damage.

Asprosin and meteorin-like protein immunoreactivity in invasive ductal breast carcinoma stages.

AIM: The study aimed to investigate asprosin (ASP) and meteorin-like (METRNL) protein immunoreactivity in invasive ductal breast cancer. MATERIALS AND METHODS: Overall, 60 cases of invasive ductal breast cancer (20 cases each of Grade 1, 2 and 3) were evaluated in addition to 20 normal breast tissues obtained from the Pathology Department Archive. ASP and METRNL expressions were assessed using immunohistochemical staining and visualised under a light microscope. RESULTS: There was a significant difference in ASP and METRNL immunoreactivity among all the groups included in the study (p < 0.001). Cancer tissues with Grade 1, 2 and 3 showed a significant increase in ASP and METRNL immunoreactivity compared with the control group; however, no significant difference was noted among the cancer tissues with Grade 1, 2 and 3. CONCLUSIONS: ASP and METRNL immunoreactivity increased at the cellular level in invasive ductal breast cancer, but there was no difference in immunoreactivity among the breast cancer grades.

RJX Improves Wound Healing in Diabetic Rats.

Background: We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats. Methods: In the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks. Findings: Notably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX - at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) - accelerates the healing of excision wounds as well burn injury in diabetic rats.

Protective effect of a novel polyherbal formulation on experimentally induced osteoarthritis in a rat model.

Osteoarthritis (OA) is a musculoskeletal disorder mainly found in elderly individuals. Modern treatment of OA, like nonsteroidal anti-inflammatory drugs, corticosteroids, hyaluronic acid injections, etc., is linked to long-term side effects. We evaluated the anti-osteoarthritic properties of a novel joint health formula (JHF) containing Bisdemethoxycurcumin enriched curcumin, 3-O-Acetyl-11-keto-beta-Boswellic acid-enriched Boswellia, and Ashwagandha in monosodium iodoacetate (MIA)-induced knee OA in rats. Twenty-eight female rats were distributed into four groups: Control, OA, OA + JHF (100 mg/kg), and OA + JHF (200 mg/kg). JHF decreased the right joint diameters but increased the paw area and stride length compared to the OA group with no treatment. JHF significantly reduced the arthritic conditions after four weeks of supplementation (p < 0.05). JHF significantly decreased TNF-α, IL-1ß, IL-10, COMP, and CRP in the serum of osteoarthritic rats (p < 0.0001). We observed reduced lipid peroxidation but increased SOD, GSH-Px, and CAT activities in response to JHF treatment in OA animals. JHF down-regulated MMP-3, COX-2, and LOX-5 and improved the histological structure of the knee joint of osteoarthritic rats. JHF demonstrated a protective effect against osteoarthritis, possibly due to anti-inflammatory and antioxidant activity in experimentally induced osteoarthritis in rats, and could be an effective option in the management of OA.

Effects of magnesium picolinate, zinc picolinate, and selenomethionine co-supplementation on reproductive hormones, and glucose and lipid metabolism-related protein expressions in male rats fed a high-fat diet.

This study aimed to examine the impacts of the magnesium picolinate (MgPic), zinc picolinate (ZnPic), and selenomethionine (SeMet) alone or as a combination on blood metabolites, oxidative enzymes, reproductive hormones, and glucose and lipid metabolism-related protein expressions in Wistar rats fed a high-fed diet (HFD). The rats were fed either a control, HFD, or HFD supplemented with a single (MgPic, ZnPic, SeMet) or two or three organic mineral combinations. Body weights, visceral fat, serum glucose, insulin, total cholesterol, triglycerides, leptin, malondialdehyde (MDA) concentrations as well as liver sterol regulatory element-binding protein-1c (SREBP-1c), liver X receptor alpha (LXRα), ATP citrate lyase (ACLY), fatty acid synthase (FAS), and nuclear factor kappa B (NF-κB) levels increased, while serum testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF-1) concentrations along with liver nuclear factor erythroid 2-related factor 2 (Nrf2) levels declined in HFD rats (P < 0.05). Supplementing each organic mineral, but particularly the combination of HFD + MgPic + ZnPic + SeMet reversed the responses with various degrees. None of the organic elements alone or as a combination of two exerted a prominent effect on parameters measured. Although not additive or synergistic, the combination of all organic minerals added to HFD (HFD + MgPic + ZnPic + SeMet) provided the greatest responses.

Effect of boron element on photoaging in rats.

BACKGROUND: The present study further assessed the effects of oral and topical applications of boron, which is known to have antiinflammatory and wound healing effects, on photoaging. METHODS: A total of 49 eight-week-old female Wistar albino rats randomly divided into seven groups (control, shaved control, shaved+UVB, topical dermabor 2% (D2), and %5 (D5), systemic sodium perborate tetrahydrate (SPT) 2% (SPT2) and 4% (SPT4). To induce an experimental photoaging, the rats were exposed to UVB at an emission spectrum of 290-320 nm. Biochemical, molecular, skin, histological, and collagen content analyzes were made at the end of the study. RESULTS: Increased skin inflammatory parameters (COX-2, IL-8, NF-KB, IL-6, and TNF-α) levels in UVB-exposed groups were inhibited in all treatment groups. The tissue level of hydroxyproline and elastase was found to decrease in all UVB-exposed group. The level of hydroxyproline was significantly higher in the D2 and D5 groups than in the SPT2 and SPT4 groups. The level of elastase was significantly lower in the D2 and D5 groups than in the SPT2 and SPT4 groups. CONCLUSIONS: In future, boron may be developed as a functionally protective treatment against photoaging caused by UVB, and may be included in sun protection systems.