Association between colorectal cancer, the frequency of Bacteroides fragilis, and the level of mismatch repair genes expression in the biopsy samples of Iranian patients.

BACKGROUND: Deficient DNA mismatch repair (MMR) can cause microsatellite instability (MSI) and is more common in colorectal cancer (CRC) patients. Understanding the carcinogenic mechanism of bacteria and their impact on cancer cells is crucial. Bacteroides fragilis (B. fragilis) has been identified as a potential promoter of tumorigenesis through the alteration of signaling pathways. This study aims to assess the expression levels of msh2, msh6, mlh1, and the relative frequency of B. fragilis in biopsy samples from CRC patients. MATERIALS AND METHODS: Based on the sequence of mlh1, msh2, and msh6 genes, B. fragilis specific 16srRNA and bacterial universal 16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: Significant increases in the expression levels of mlh1, msh2, and msh6 genes were observed in the cancer group. Additionally, the expression of these MMR genes showed a significant elevation in samples positive for B. fragilis presence. The relative frequency of B. fragilis in the cancer group demonstrated a significant rise compared to the control group. CONCLUSION: The findings suggest a potential correlation between the abundance of B. fragilis and alterations in the expression of MMR genes. Since these genes can play a role in modifying colon cancer, investigating microbial characteristics and gene expression changes in CRC could offer a viable solution for CRC diagnosis.

Comparison of the Effects of Rosmarinic Acid and Electromagnetic Radiation-Induced Cardiotoxicity on Rats.

Background: Electromagnetic radiation (EMR) causes stable aggregation of reactive oxygen species (ROS), producing oxidative stress. Rosmarinic acid (RA), a plant-origin antioxidant, has been proposed against the side effects of cell phone and ultrahigh-frequency waves. Methods: Forty-two male Wistar rats were randomly divided into 6 groups. Group 1 (controls) received 5 mL of normal saline with the gavage method, Group 2 received 915 MHz radiation, Group 3 received 2450 MHz radiation, Group 4 received RA plus 915 MHz radiation, Group 5 received RA plus 2450MHz radiation, and Group 6 received oral RA (5 mg/kg). Treatment and radiation (1 hour per day) continued for up to 30 days. Results: EMR significantly reduced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), the content of glutathione (GSH), and the level of total antioxidant capacity (TAC) and significantly increased oxidative stress indices, such as the levels of malondialdehyde (MDA) and nitric oxide (NO), and the content of protein carbonyl (PC). In contrast, RA significantly elevated TAC level (all groups), GSH content (the RA/cell phone radiation group), GPx activity (the RA/ultrahigh-frequency radiation group), SOD activity (all groups), and CAT activity (RA/ultrahigh-frequency radiation group) and conversely reduced MDA level (all groups), NO level (all groups), and PC content (all groups) in the RA/cell phone and RA/ultrahigh-frequency radiation groups compared with the NS/cell phone and NS/ultrahigh-frequency radiation groups, respectively. The administration of RA resulted in a significant reversal of cardiac markers in EMR-intoxicated rats. Conclusion: RA treatment showed a significant protective effect against EMR-induced cardiotoxicity.

Investigating the effect of the inhibitory peptide on L.monocytogenes cell invasion: an in silico and in vitro study.

AIMS: L.monocytogenes monocytogenes is an omnipresent bacterium that causes a fatal food-borne illness, listeriosis. The connection of this bacterium to E-cadherin through internalin A plays a significant role in the internalization of the bacteria. In this study, this interaction has been investigated for the design of an inhibitory peptide. METHODS: The interaction of the proteins involved in the entry of bacteria was evaluated by molecular docking. According to their interactions, an inhibitory peptide was designed to bind to internalin A by server peptiderive. Its effects on L.monocytogenes invasion on the Caco-2 cell line and biofilm formation were also assessed. FINDINGS: Docking results showed that the peptide has a high affinity for binding to Internalin A. The synthesized peptide at a concentration of 64 µg/ml inhibited 80% of the invasion of L.monocytogenes into the Caco-2 cell line. Furthermore, the studied peptide at the highest concentration had a slight inhibitory effect on biofilm formation. CONCLUSION: These results reveal that short polypeptides can impede the invasion of target cells by L. monocytogenes in vitro and could be advantageous as restoring agents in vivo.

Gentisic acid mitigates gentamicin-induced nephrotoxicity in rats.

The current investigation was considered to evaluate the beneficial effects of gentisic acid (GA) on gentamicin (GEN)-induced nephrotoxicity in rat kidneys through assessment of oxidative stress, inflammatory cytokines, and histopathological changes. Rats were split into five equal groups. Rats were treated with GA (25, 50, and 100 mg/kg/day, p.o.) for 14 consecutive days and GEN (100 mg/kg, i.p.) was administrated from day 8 to day 14 of the experiment. On the 15th day, blood samples were collected to determine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cr) levels. Malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß), and nitric oxide (NO) levels and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were assessed in the renal tissue. Histopathological evaluations were done to confirm the biochemical results. GEN increased the levels of NGAL, KIM-1, BUN, and Cr in serum as well as MDA, NO, GSH, TNF-α, and IL-1ß in renal tissue. Moreover, GEN administration reduced the activity of CAT, SOD, and GPx in renal tissue. Nonetheless, the administration of GA before and alongside GEN mitigated these deleterious effects. In conclusion, GA has a beneficial effect on biochemical, inflammatory, and oxidative stress indices against GEN-induced nephrotoxicity.

Association between colorectal cancer and expression levels of miR-21, miR-17-5P, miR-155 genes and the presence of Fusobacterium nucleatum in biopsy samples obtained from Iranian patients.

BACKGROUND: Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC. METHOD: DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method. RESULTS: The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group. CONCLUSION: Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes.

Gemfibrozil palliates adriamycin-induced testicular injury in male rats via modulating oxidative, endocrine and inflammatory changes in rats.

Adriamycin (ADR), an antineoplastic drug, is widely used to treat different types of cancers. Yet, the usage is limited because of its severe side effects on testis. On the other hand, gemfibrozil (GEM), as an anti-hyperlipidemic drug, has other pharmacological effects independent of lipid- lowering activity including anti-inflammatory and antioxidant properties. The present experiment was designed to investigate the effect of GEM on ADR-induced testicular injury in male rats. A total of 28 male Wistar rats were divided into 4 equal groups: Control; ADR; ADR + GEM; GEM. Serum level of testosterone, luteinizing hormone and follicle stimulating hormone were assessed. Also, testicular tissue oxidant/antioxidant markers (malondialdehyde, total antioxidant capacity, nitric oxide, superoxide dismutase, catalase, glutathione peroxidase and glutathione) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) were measured. Histopathological studies were conducted on testes. GEM improved hormonal profile and antioxidant defenses in comparison with ADR-treated animals. GEM, significantly reduced the production of proinflammatory cytokines compared with ADR-treated animals. Hormonal and biochemical results were further supported by testicular histopathological findings. Thus, GEM might represent a promising therapeutic modality for the attenuation of testicular injury induced by ADR in clinic.

Accuracy of diagnostic assays for the detection of Clostridioides difficile: A systematic review and meta-analysis.

INTRODUCTION: Clostridioides difficile Infection (CDI) has been identified as one of the main causes of nosocomial infection all across the world. Rapid diagnosis of CDI is difficult and poses a significant challenge to physicians worldwide. We undertook a systematic review and meta-analysis to evaluate rapid tests' diagnostic accuracy against toxigenic culture as the reference standard for CDI. METHOD: We searched the PubMed/MEDLINE and EMBASE databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures [i.e., sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and the area under the curve (AUC)] were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (Version 1.4, Cochrane Colloquium, Barcelona, Spain) and RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark). RESULTS: We reviewed retrieved records and identified 63 studies that met the inclusion criteria. 26 were about enzyme immunoassay (EIA) (our main index test). The sensitivity of GDH and Tox A/B EIAs were 82% (95% CI: 79-84) and 75% (95% CI: 70-79), respectively. On the other hand, the specificity of GDH EIA was 91% (95% CI: 90-92) and the specificity of Tox A/B EIA was 95% (95% CI: 94-96). Among other index tests, BD Max with 92% has the most sensitivity and cell cytotoxicity neutralization assay (CCNA) has the most specificity (100%). CONCLUSION: This meta-analysis demonstrated that EIAs could be reliable methods for detecting CDI based on their sensitivity, specificity, time and cost-effectiveness, and simplicity in the procedure. Further work to improve rapid tests would benefit from improvements to the methodology.

Diosmin prophylaxis reduces gentamicin-induced kidney damage in rats.

Gentamicin is an essential aminoglycoside antibiotic, but it is only used to treat severe bacterial infections due to its high nephrotoxicity in patients. We evaluated the preventive effects of diosmin (as a natural ingredient) on gentamicin-related kidney damage in rats. In this research, 28 male Wistar rats were divided into four groups: control, gentamicin (100 mg/kg (i.p.), daily for 1 week), gentamicin plus diosmin (50 mg/kg, p.o., daily for 2 weeks), and diosmin (50 mg/kg/day, p.o. for 2 weeks). After the final gavage, blood samples were collected for the determination of blood urea nitrogen (BUN) and creatinine. Kidneys are used for biochemical, inflammatory, and histological tests. The concentrations of creatinine, BUN, nitric oxide, malondialdehyde, tumor necrosis factor α (TNF-α), and interleukin 1 beta (IL-1ß) were significantly increased. But, the level of glutathione and activities of catalase, glutathione peroxidase, and superoxide dismutase decreased during treatment with gentamicin. On the other hand, the concentrations of creatinine, BUN, nitric oxide, malondialdehyde, TNF-α, and IL-1ß were significantly reduced, and the glutathione level, activities of catalase, and glutathione peroxidase were significantly increased via co-administration with diosmin. Diosmin had ameliorative impacts against gentamicin-related kidney injury due to its antioxidant and anti-inflammatory activities.

Immunopotentiating properties of chimeric OprF-OprI-PopB protein against Pseudomonas aeruginosa PAO1 in the infected burned rat model.

Objectives: Pseudomonas aeruginosa, as an opportunistic pathogen, is known to cause nosocomial infections among patients suffering from burn injuries and also cystic fibrosis patients. The objective of our research was to develop a novel vaccine against P. aeruginosa. Materials and Methods: A recombinant P. aeruginosa subunit vaccine based on the outer membrane proteins, including the OprF-OprI region and its major protein in the type III secretion system, PopB (called FIB protein) was formulated. To induce a robust immune response, our preferred regions were conjugated to a carrier protein, GMCSF (Granulocyte-macrophage colony-stimulating factor). FIB protein's immunogenicity with and without adjuvant was evaluated in vaccinated rats and also burned rat models, which were subcutaneously challenged by the PAO1 strain of P. aeruginosa. Results: Antibody levels were increased in sera of rats in this study. Assessment of the resident memory CD4+ T cells in splenocytes from vaccinated rats demonstrated that the FIB conjugated with GMCSF could cause higher responses in comparison with other groups. Moreover, immunization with the FIB plus adjuvant protein could improve interferon-gamma (IFN-γ) production, interleukin 17A (IL-17A), and IL-4, contributing to elicit humoral and cellular immune responses and decreased post-infection bacterial loads after PA challenge, pathology, and inflammatory cell infiltration. Conclusion: These observations demonstrated that FIB conjugated with GMCSF can be a putative vaccine candidate against P. aeruginosa in burnt rat models.

Neuroprotective effects of tannic acid against kainic acid-induced seizures in mice.

BACKGROUND: Epileptic seizures are associated with the release of potentially neurotoxic amount of glutamate, which results in the over-production of free radicals and inflammatory factors, and induction of neuronal cell death. Current study evaluated the effect of tannic acid (TA) on Kainic acid (KA)-induced seizures in mice. METHODS: Mice were divided into the six groups. Group I was administrated with normal saline (NS; 1 mL/kg, intraperitoneally (i.p.)), Group II was injected with KA (15 mg/kg, i.p.), Groups III was treated with diazepam (DZ; 20 mg/kg, i.p.) and KA (15 mg/kg, i.p.), Groups IV-VI were treated with TA (25, 50 and 100 mg/kg, i.p.) and KA (15 mg/kg, i.p.). Animals received all treatments 30 min before injection of KA. After the injection of KA, mice were observed for seizure (latency, activity and duration) and mortality for 2 h. In the brain tissue, oxidative stress, apoptosis, and inflammatory markers were evaluated in addition to the determination of histological alterations in the CA1 molecular layer of hippocampus. RESULTS: Treatment with TA significantly increased seizure latency and decreased seizure duration and activity, but could not significantly decrease mice mortality. This effect was associated with the reduction of oxidative stress, inflammation, and apoptosis. Furthermore, treatment with TA significantly improved KA-induced pyramidal cell loss and change in the arrangement of CA1 molecular layer. CONCLUSIONS: Tannic acid may be useful in the control of epileptic seizures through regulating oxidative stress, inflammation and apoptosis.

Gallic acid ameliorates di-(2-ethylhexyl) phthalate-induced testicular injury in adult mice.

Background: Di-(2-ethylhexyl) phthalate (DEHP) is a well-known endocrine-disrupting compound inducing degeneration of testes. Gallic acid (GA) is a polyphenol with various pharmacological properties, including antioxidant and anti-inflammatory effects.Purpose: This research evaluated effects of different doses of GA on DEHP-induced testicular injury in adult mice.Research Design: Male mice were randomly divided into five groups and treated with agents for two weeks; group (I) received normal saline and corn oil (5 mL/kg/day, p. o.), group (II) received DEHP (2 g/kg/day, dissolved in corn oil, p. o.), groups (III, IV, and V) received DEHP + GA (25, 50, and 100 mg/kg/day, p. o.). Body and testes weights, serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were evaluated. The number of sperms and sperm motility and viability were analyzed in the cauda epididymis. Histological changes, oxidative/nitrosative stress markers, and inflammatory cytokines levels were examined in testes.Results: Body and testes weights, the number of spermatogonia, primary spermatocyte and early spermatid, and late spermatid and sperm vitality, and progressive motility were significantly reduced in mice exposed to DEHP. Serum testosterone level decreased and serum LH and FSH levels increased in DEHP-exposed mice. These alterations were associated with the increased oxidative stress level and inflammatory responses in testicular tissue. Treatment with GA (50 and 100 mg/kg/day) attenuated DEHP-induced alterations in oxidative stress markers and inflammatory cytokines and reversed abnormality in sperm characteristic and number, tissue structure, and serum hormones levels.Conclusions: Results indicated that GA might be a promising agent against male gonadal toxicity induced by endocrine disrupting chemicals including DEHP.

Isolation and Chemical Characterization of an Alpha-Helical Peptide, Dendrocin-ZM1, Derived from Zataria multiflora Boiss with Potent Antibacterial Activity.

Today, resistance of microorganisms to antibiotics has become a major challenge. To overcome this problem, development of new drugs, besides research on their antibacterial activity, is essential. Among chemical components, antimicrobial peptides (AMPs) exhibit antibacterial activity and can be selected as suitable antimicrobial candidates. In this study, a novel antimicrobial peptide, called dendrocin-ZM1, with a molecular weight of ~3716.48 Da, was isolated from Zataria multiflora Boiss (ZM) and purified via precipitation with ammonium sulfate and reverse-phase HPLC chromatography; it was then sequenced via Edman degradation. The in silico method was used to examine the physicochemical properties of dendrocin-ZM1. In this study, four reference strains (gram-positive and gram-negative) and one clinical vancomycin-resistant Staphylococcus aureus strain were used to survey the antimicrobial activities. Moreover, to examine cytotoxicity and hemolytic activity, a HEK-293 cell line and human red blood cells (RBCs) were used, respectively. Evaluation of the physicochemical properties of dendrocin-ZM1, as an AMP, indicated a net charge of + 7 and a hydrophobicity percentage of 54%. This peptide had an amphipathic alpha-helical conformation. It exhibited broad-spectrum antibacterial activities against the tested strains at minimum inhibitory concentrations (MICs) of 4-16 µg/mL. Besides, this peptide showed negligible hemolysis and cytotoxicity in the MIC range. It also exhibited heat stability at temperatures of 20 to 80 °C and was active in a broad pH range (from 6.0 to 10.0). Overall, the present results suggested dendrocin-ZM1 as a remarkable antimicrobial candidate.

Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice.

PURPOSE: Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. METHODS: Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1ß) levels as inflammatory mediators were assessed in kidney tissue. RESULTS: The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1ß and increasing the level of GSH, CAT, SOD, and GPx activities. CONCLUSION: Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats.

Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.

Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.

BACKGROUND: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects. OBJECTIVE: The current research aimed at evaluating the GA effect on CP-related renal toxicity. METHODS: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1ß, TNF-α levels were assessed in renal tissue. RESULTS: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1ß, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect. CONCLUSION: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat

Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.

Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Oxidative stress and inflammation influence the occurrence of BPH. Berberine (BBR) is a natural ingredient that has antioxidant and anti-inflammatory properties. The current research aims at examining the effects of BBR on testosterone-stimulated BPH in rats. METHODS: Animals were randomly categorized to six groups. In the control group, normal saline and olive oil were injected as the vehicle. BPH group: received testosterone (3 mg/kg, subcutaneous, 28 days), BPH + BBR groups; received BBR (25 and 50 mg/kg, p.o, 28 days), BPH + finasteride groups: received finasteride (1 mg/kg, p.o, 28 days), BBR (50 mg/kg, p.o, alone) was administered for subjects in the BBR group. On the 29th day, after anesthesia, cervical dislocation was used to kill the subjects. Serum concentration of testosterone and dihydrotestosterone was measured and prostate tissues were excised and used for biochemical, inflammation, and histological analysis. RESULTS: BBR prevented increased serum concentrations of testosterone and dihydrotestosterone. BBR considerably reduced BPH-stimulated oxidative stress and inflammation through preventing the rise in lipid peroxidation and nitrite concentration and declined the accumulations of pro-inflammatory cytokines (e.g. interleukin 1ß and tumor necrosis factor α) and declining the depletion rate of GSH and the function of catalase and superoxide dismutase. Histopathological investigations reported that administration of BBR could suppress testosterone-stimulated BPH. CONCLUSION: This study demonstrated that BBR could significantly prevent the development of BPH in rats.

Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats.

AIMS: Bleomycin, an important toxic anti-cancer agent, induces pulmonary fibrosis. The significance of oxidative stress and inflammation in promoting of bleomycin-induced idiopathic pulmonary fibrosis (IPF) has been reported. Thus, we evaluated the protective effects of carnosol as a robust natural antioxidant and anti-inflammatory agent for bleomycin-related IPF in rats. MAIN METHODS: Male Wistar rats (n = 40) were randomly assigned to five groups. Group 1 was administrated with saline (intratracheally) on day 7 and oral gavage of dimethyl sulfoxide (DMSO, 0.05%) from day 1 to day 28. Group 2 received a single dose of bleomycin (intratracheally, 7.5 UI/kg) on day 7 and oral gavage of saline for 28 days. Groups 3, 4 and 5 were administrated with bleomycin (single dose) on day 7, along with oral administration of carnosol (at doses 10, 20 and 40 mg/kg, respectively) from day 1 to day 28. The lungs were isolated to measure the histopathological and biochemical and inflammatory markers. KEY FINDINGS: Carnosol treatment significantly reduced malondialdehyde, nitric oxide, protein carbonyl, tumor necrosis factor- α, interleukin-6 levels and myeloperoxidase activity in the lungs of rats exposed to bleomycin. Also, lung glutathione content, catalase, glutathione peroxidase and superoxide dismutase activities significantly increased in the carnosol/bleomycin-treated group than the bleomycin group. Lung index, hydroxyproline content, fibrosis and histopathological changes, also significantly decreased by carnosol therapy. SIGNIFICANCE: Treatment with carnosol can modulate biochemical and histological alterations caused by bleomycin. Thus, it can be regarded as an appropriate therapeutic approach for IPF.

Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation.

BACKGROUND: We aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA). MATERIALS & METHODS: We have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals' bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment. RESULTS: CHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner. CONCLUSION: The results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

Characterization, Biological Activity, and Mechanism of Action of a Plant-Based Novel Antifungal Peptide, Cc-AFP1, Isolated From Carum carvi.

Due to the increasing rate of invasive fungal infections and emerging antifungal resistance, development of novel antifungal drugs has been an urgent necessity. Antifungal peptides (AFPs) have recently attracted attention due to their unique ability to evade drug-resistant fungal pathogens. In this study, a novel AFP, Cc-AFP1, with a molecular weight of ~3.759 kDa, was isolated from Carum carvi L., purified by ammonium sulfate precipitation and reversed-phase HPLC and finally identified by sequence analysis using Edman degradation. Peptide sequence analysis revealed a fragment of 36 amino acid residues as RVCFRPVAPYLGVGVSGAVRDQIGVKLGSVYKGPRG for Cc-AFP1 with a net charge of +5 and a hydrophobicity ratio of 38%. The antifungal activity of Cc-AFP1 was confirmed against Aspergillus species with MIC values in the range of 8-16 µg/ml. Cc-AFP1 had less than 5% hemolytic activity at 8-16 µg/ml on human red blood cells with no obvious cytotoxicity against the HEK293 cell line. Stability analysis showed that the activity of Cc-AFP1 was maintained at different temperatures (20°C to 80°C) and pH (8 to 10). The results of a propidium iodide uptake and transmission electron microscopy showed that the antifungal activity of Cc-AFP1 could be attributed to alteration in the fungal cell membrane permeability. Taken together, these results indicate that Cc-AFP1 may be an attractive molecule to develop as a novel antifungal agent combating fungal infections cause by Aspergillus species.