Biomedicine & Aging Pathology最新文献

This study investigated the effect of N-acetylcysteine (NAC) against γ-radiation-induced cytotoxicity in human hepatocellular carcinoma (HepG2) cells. HepG2 Cells were incubated with 20 mM of NAC for 24 h prior to 6 Gy γ-irradiation. Apoptosis markers, such as caspase-3 and DNA fragmentation and oxidative stress markers, such as total nitrate/nitrite (NO(x)) and malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione (GSH) content were studied. Half of the lethal dose (LD₅₀) of NAC on HepG2 cell viability was found to be 20 mM/mL after incubation for 48 h. Incubation of irradiated HepG2 cells with NAC inhibited γ-radiation-induced increases in caspase-3 activity and DNA fragmentation. Treatment with NAC before γ-radiation restored the changes induced by γ-irradiation by increasing SOD activity and GSH content in parallel with a decrease in MDA and NO(x) levels in HepG2 cells. NAC has a modulatory effect against γ-radiation-induced oxidative damage plausibly ascribable to its antioxidant/free radical scavenging ability.

Garcinia indica Choisy (Family: Guttiferae/Clusiaceae) is a slender evergreen tree endemic to the west coast of India. The dried rind of the fruit of Garcinia indica known as “kokum” is an Indian spice and a food additive. Many therapeutic effects of the fruit have been reported in literature. The present study evaluates the antiulcer activity of the aqueous extract of Garcinia indica fruit rind (GIE) against absolute ethanol- (necrotizing agent), aspirin- (non-steroidal anti-inflammatory drug) and histamine- (gastric secretion stimulator via H₂ receptor) induced ulcers in rats. GIE (400 mg/kg and 800 mg/kg) was administered orally to the overnight fasted rats, 1 h prior to the absolute ethanol/aspirin/histamine challenge. The ulcer index, gastroprotective potential, status of the antioxidant enzymes {superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)} along with reduced glutathione (GSH), and lipid peroxidation were studied in all the three models. Pre-treatment with GIE showed a dose-dependent decrease in the ulcer index in all three models. GIE, at both doses, elicited significant antioxidant activity by attenuating the ulcer elevated levels of MDA and restored the ulcer-depleted levels of GSH, SOD, CAT, GPx and GR. In conclusion, GIE possesses potent antiulcer activity, which may be attributed to an underlying antioxidant activity.

Recently, considerable attention has been paid to utilize biofriendly and ecofriendly plant-based products for the prevention, cure and treatment of neurodegenerative disease. This article reviews herbs that have been documented to have a neuroprotective effect in vitro and in vivo Parkinson's disease (PD) model systems. We summarized the anti-Parkinsonian activities of herbs according to their genera. Plants corresponding to 47 genera were included in this review. These herbal medicines can be a substitute and precious source for anti-Parkinsonian drug discovery. The plant species in these families and genera whose pharmacological actions have been well characterized could possibly be good candidates for further studies to assess its ability to protect against neurodegenerative disease and potentially extend lifespan.

In this research, we have conducted docking study to screen bioactive compounds from Microcystis aeruginosa and Phormidium corium. Among the two blue-green algal species were analyzed for chemical nature of bioactive substances using TLC and GC-MS methods. The antimicrobial compounds identified were phenolics, alkaloids, steroids. In the present study as reported that M. aeruginosa curde extract contained the bioactive compound Microginins, while Cyalobolide B was detected from P. corium. The phytochemical analysis of M. aeruginosa (Microginins), provided ethaneloic acid, Octanal, 3,7,11-Trimethyl-1,6,10-dodecatrien-3-ol (nerolidal), Monomethyl hydrazine and formic acid. The cumulative effect of these phytochemical provided more effective antimicrobial compound in inhibiting microbial growth. The phytochemical analysis of P. corium (Cyalobolide B) exhibited Ethaneloic acid, Dihydrodiplodialide, 3, 7, 11-Trimethyl-1, 6, 10-dodecatrien-3-ol (nerolidal), 1-Dodecanol, 1-Hexadecanol (CAS) and nanonic acid. These compounds together exhibited more effective antimicrobial substance in inhibiting microbial growth. Which members of a community interact with themselves as well as with different host structures and components of Candida albicans and Streptococcus mutans. The pathogenesis of this dental infection is a multi factorial process that results in a serious degenerative disease of the Oral candidiasis. In the present study SAP (secreted aspartyl proteinases in virulence and pathogenesis) is taken as a case study molecule to understand high reactive responses of various drugs administered for the oral candidiasis. The drugs are being compared with the SAP from C. albicans and SpaP (cell surface antigen SpaP gene) from S. mutans. The SAP and SpaP interacted with formic acid, nerolidal, octanol and nonanoic acid using docking methods. The exponentially increasing speed of computational methods makes a more extensive use in the early stages of drug discovery attractive if sufficient accuracy can be achieved.

Aspartame was approved by the U.S. Food and Drug Administration (FDA) in 1981 for dry food in 1983 for soft drinks and in 1996 for all foods. In 2006, it was approved for use throughout the European Union [EFSA] on safety dose (40 mg/kg b.w). The artificial dipeptide sweetener aspartame [APM; L- aspartyl-L- phenylalanine methyl ester] is present in many products especially unsweetened and sugar products. These products are frequently utilized by people trying to lose weight or patients with diabetes. Concern relating to the possible adverse effect has been raised due to aspartame metabolic components. Aspartame is rapidly and completely metabolized in humans and experimental animals to aspartic acid (40%), phenylalanine (50%) and methanol (10%). Methanol, a toxic metabolite is primarily metabolized by oxidation to formaldehyde and then to formate these processes are accompanied by the formation of superoxide anion and hydrogen peroxide. This study focus is to understand whether the oral administration of aspartame (40 mg/kg b.w.) for 90 days, have any effect on membrane bound ATPase's, which may cause ionic disproportion and imbalance the homeostasis of immune organs in wistar albino rats. To mimic human methanol metabolism, folate deficient rats were used. After 90 days of aspartame administration, showed a significant alteration in membrane bound ATPase's and serum ions. Excess free radical generation is confirmed by increase in lipid peroxidation and nitric oxide level. This study concludes that oral administration of aspartame (40 mg/kg b.w.) for longer duration altered the homeostasis of immune organs, may cause oxidative stress in immune organs of wistar albino rats.

Gemcitabine and cisplatin regimen is an approach currently used in urinary bladder cancer treatment. However, side effects’ arising from its administration is a hard concern. In this study, we evaluated different schedules of gemcitabine and cisplatin to determine the efficacy of this combination together with two mammalian targets of rapamycin (mTOR) inhibitors: temsirolimus and everolimus. The 5637, HT1376 and T24 urinary bladder cancer cell lines were exposed to gemcitabine (72 hours), cisplatin (48 hours), temsirolimus (72 hours) and everolimus (72 hours), in isolation, or in combined schedules (gemcitabine, cisplatin and temsirolimus, or gemcitabine, cisplatin and everolimus). The levels of phosphorylated p70S6 K and 4E-BP1 after treatment with temsirolimus and everolimus were investigated by immunoblotting. The antiproliferative activity, cell cycle distribution, autophagy and apoptosis were analyzed by the MTT assay and immunocytochemistry, flow cytometry, acridine orange staining and M₃₀ CytoDEATH antibody. No significant differences in the expression of P-4E-BP1 and P-p70S6 K after temsirolimus and everolimus exposure were found in the HT1376 and T24 cell line. A statistically significant decrease of phosphorylated 4E-BP1 form was detected in the 5637 cell line (P < 0.05) after everolimus exposure. Temsirolimus and everolimus conjugated with gemcitabine and cisplatin decreased the cell proliferation in all three cell lines. This pattern of response was similar to the other parameters analyzed (reduced Ki-67 expression, increased autophagy and apoptosis). Also, in the combined regimen, an enhanced cell cycle arrest in the G₀/G₁ phase in the 5637 cell line and in the early S-phase in the HT1376 and T24 cell lines were observed. The muscle invasive HT1376 and T24 cell lines were the most sensitive to both combinations. The combination of gemcitabine, cisplatin and temsirolimus or everolimus yields an enhanced cytotoxicity efficacy, namely in the muscle invasive urinary bladder cancer cell lines. Although further studies are necessary to complement this data, the present results opening new perspectives in muscle invasive urinary bladder cancer treatment.

A total of 60 healthy pesticide sprayers (smokers and non-smokers) in cotton fields exposed to different classes of pesticides for many years were compared with controls matched for age with respect to serum cholinesterase (ChE), serum total protein, alkaline and acid phosphatases (ALP and AP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), creatine kinase (CK), blood glucose, serum hormones FSH, testosterone and L-thyroxine (T4). Significant increase was observed in serum ALP, AP, LDH, GGT, CK, serum hormones FSH, testosterone, L-thyroxine and blood glucose. Significant decrease in serum total protein and ChE. The increase or decrease in the tested biomarkers was more pronounced in the smokers than non-smoker workers. These results suggest that the long-term exposure of various pesticides on sprayers of cotton fields affect the normal functioning of different organ systems and may produce characteristic clinical effects.

Aim of the study

To investigate anti-arthritic activity of methanolic extract of Cyathocline purpurea (MECP) in Freund's complete adjuvant (FCA)-induced arthritis in rats.

Methods

The MECP was prepared and subjected to acute oral toxicity in mice and tested against FCA induced arthritis in rats. Arthritis assessment was done by measuring – paw volume, joint diameter, pain threshold, thermal hyperalgesia, mechanical nociceptive threshold and body weight. Haematological, serum, biochemical and in vivo anti-oxidant parameters were measured on the last day of the study. Histopathological and radiological analyses of ankle joints were also done. MECP was administered at the dose of 100, 200 and 400 mg/kg body weight.

Results

MECP dose dependently showed anti-arthritic activity which was evident with decrease in paw volume, joint diameter and increase in pain threshold, paw withdrawal latency, mechanical nociceptive threshold and body weight when compared to arthritic control group. MECP (400 and 200 mg/kg) exhibits significant (P < 0.001 and P < 0.01, respectively) anti-arthritic activity by increasing levels of RBC, Hb and by decreasing levels of WBC, platelets and also serum C-reactive protein (CRP) and Rheumatoid factor (RF). The anti-arthritic activity was also confirmed with the altered biochemical parameters (AST, ALT, ALP and total protein level) and anti-oxidant parameters (SOD, MDA and GSH). MECP (400 and 200 mg/kg) and diclofenac (10 mg/kg) also inhibited joint destruction (histopathological and radiological analysis).

Conclusion

C. purpurea may be a potential preventive or therapeutic candidate for the treatment of inflammation and arthritis.

Aim of the study

The stem bark of tree Ficus bengalensis Linn (Moraceae) is known to induce anti-inflammatory activity and also used for the treatment of inflammatory diseases in Indian traditional system of medicine. Therefore, in the present study, its anti-arthritic activity was evaluated and compared with methotrexate, dexamethasone and diclofenac sodium, using experimentally induced arthritic animal models.

Materials and methods

The methanolic extract of Ficus bengalensis (MEFB) was studied in formalin and Complete Freund's adjuvant (CFA) induced arthritis in rats using relevant biological and biochemical parameters, viz. paw edema volume, arthritic score, oxidative stress biomarkers [lipid peroxidation, nitric oxide (NO), antioxidants (enzymatic and non-enzymatic), serum lysosomal enzymes (AST, ALT and LDH), connective tissue biomarkers (hydroxyproline, sialic acid and glucosamine), pro-inflammatory mediators (TNF-α and IL-6)] and radiographic pattern of hind legs.

Results

Treatment with MEFB, methotrexate, diclofenac and dexamethasone elicited reduction in paw edema and arthritic score, amelioration of oxidative stress, prevention of elevation of LPO and NO, restoration of antioxidants (in edematous and liver tissues), inhibition of serum lysosomal enzymes, biomarkers of connective tissue, and pro-inflammatory cytokines along with improvement of radiographic features of hind legs. Further, MEFB reduced acetic acid induced pain syndrome in mice. Evaluation of our experimental findings suggests that anti-arthritic activity of MEFB (400 mg/kg) was slightly better than diclofenac sodium and less than that of methotrexate and dexamethasone.

Conclusion

The antioxidant property of MEFB may largely be responsible for its anti-arthritic activity, and can be a feasible therapeutic candidate for the treatment of chronic arthritis.

The chemokine CXCL12 (SDF-1) is an extracellular chemokine which binds to its cell surface receptor CXCR4. The axis of CXCL12/CXCR4 has been considered to play an important role for cancer cell migration. Recently, the aberrant expression of CXCR4 has been found during the malignancy of colorectal cancer (CRC), where it plays a crucial role in, among others, the proliferation, angiogenesis and metastatic spread. Various intracellular signal transduction cascades and effectors related to the CXCR4/CXCL12 axis have been determined, such as MAPK, PI-3K/Akt and Wnt. Currently, the potential role of CXCR4/CXCL12 as the therapeutic target for treatment of CRC has been focused. In this review, we summarized recent research on CXCL12/CXCR4 axis in the development of CRC.