Biomedicine & Aging Pathology最新文献

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.

The present experimental study is to investigate the efficacy of some phytochemicals on heavy metal intoxicated animals. Commonly phytochemicals have played a vital role for protective effect of oxidative stress, which is induced by heavymetals in animals. At sub-lethal dose of mercuric chloride (1.23 mg/kg body weight) treated rat liver tissue shows hepatic cell damage and alteration of its metabolic activities by the way of liver marker enzymes. The hepato-protective effect of Hesperidin and ellagic acid was tested against mercuric chloride induced hepato-toxicity in rats. In the present study, drastically altered in the level of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Lactic dehyrogenase (LDH), bilirubin, albumin, cholesterol, urea and creatinine levels were observed in the blood serum of mercury intoxicated rats. The activity of liver marker enzymes such as ALT AST, ALP and LDH were significantly increased and albumin was simultaneously decreased in mercuric chloride intoxicated rats. Administration of Hesperidin and Ellagic acid (5 mg/kg body weight) on mercuric chloride intoxicated rats not only reduced the liver markers enzymes and bilirubin and cholesterol levels and also maintain their level to near normal condition. Hesperidin and ellagic acid alone treated animals did not alter the ALT, AST, ALP, LDH, bilirubin, albumin, cholesterol urea and creatinine levels in serum. Our results indicate that treatment for hesperidin and ellagic acid exhibited the strong hepatoprotective activity against mercuric chloride induced hepatotoxicity.

Thalidomide is one of the anti-angiogenic drugs, which have been investigated as a possible treatment for various cancers and diseases. This work aimed to study novel thalidomide analogs for their anti-cytotoxicity, anti-angiogenic, treratogenic gene (FGF-2) expression as well as changes in histone deacetylase (HDAC) activity and nuclear factor kappa-B (NF-κB) level using two different cancer cell lines (Hep-G2 and MCF-7 cells). MTT assay was used to assess the cytotoxic effect of thalidomide analogs against Hep-G2 and MCF-7 cells. HDAC activity was estimated by colorimetric assay. NFκB- P65, pro-angiogenesis and anti-angiogenesis markers were determined by Enzyme-linked immunosorbent assay (ELISA). FGF-2 expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Thalidomide dithiocarbamate analogs 1, 5 and thalidomide dithioate analog 3 showed elevation in their cytotoxic activity better than thalidomide. Thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 showed reduction in pro-angiogenic and elevation of anti-angiogenic factors in both cell lines; furthermore, analog 1 is the most potent analog in MCF-7 cells as an anti-angiogenic agent. In Hep-G2 cells, analogs 1, 2, 4 showed a significant increase while analogs 3 and 5 induced a significant decrease in NF-κB level in relation to thalidomide. A drastic decline in HDAC activity was demonstrated in the following order 2 > thalidomide > 1 > 3 > 5 > 4 of the control activity. In conclusion, this study showed that thalidomide analogs are more potent anti-tumor agents with more pronounced effect by working selectively on specific types of tumors than thalidomide.

Herbal medicines are gaining growing interest because of their cost-effective, eco-friendly attributes and true relief from disease condition. Sarcostemaacidum was documented in many folklore practices for various psychiatric conditions. It has been dealt with in detail in “SHRUSHRUTHA SAMHITHA”. Ethyl acetate extract of the whole plant Sarcostemaacidum (EASA) was evaluated for psychopharmacological effects, anti-psychotic, anxiolytic and CNS inhibitory activity. Anti-psychotic effects of EASA was assessed by condition avoidance response and Cataleptic scoring test using pole climbing and Bar test respectively. Elevated Plus maze (EPM) and Hole Board Apparatus (HBA) was employed for the anxiolytic activity while actophotometer was used to assess the CNS inhibitory activity. EASA (650 mg/kg), haloperidol (5 mg/kg) and 1% CMC was administered to the test,standard and control group respectively for Antipsychotic activity, while for anxiolytic and CNS depressant studies test, standard and control group receive EASA(650 mg/kg), diazepam (2 mg/kg) and 1% CMC respectively. It was found that EASA significantly enhance the latency period to climb the pole and the cataleptic score which indicates its suppression on CAR activity, which clearly confirms its anti psychotic activity, might be due to blockade of dopaminergic pathway. It was observed that EASA at a dose of 650 mg/kg significantly increases the no. of entries in to the open arm in EPM as well as no. of head poking in HBA, which reflects its increase in exploratory behaviour which indicates the anxiolytic activity. Reduction in the locomotor activity in actophotometer indicates CNS depressant property of the drug.

Cushing's syndrome (CS) is caused by excessive exposure to glucocorticoids, and the initial tests for diagnosis (urine free cortisol [UFC], late-night salivary cortisol, overnight low-dose dexamethasone suppression test [LDDST]) should be performed for patients. However, such test is burdensome and costly to patients, that is, not so easy examination. Therefore patients with CS can be underdiagnosed in general practice. If not diagnosed and treated appropriately, it can be lethal. The aim of our study was to establish a new method of assisting detection of CS patients using an appropriate set of routine clinical tests, similar to our successful previous works about screening patients with thyroid dysfunction. Thirty patients with CS and 49 healthy individuals were included in the present study. An optimal set of routine clinical tests (a new effective marker) to screen patients with CS was identified and the association of these clinical tests with serum cortisol levels was established by using pattern recognition methods. Serum cortisol was highly associated with a combination of 8 characteristics (γ-GTP, LDH, Na, K, and counts of neutrophils, lymphocytes, eosinophils and monocytes) in patients with CS. Their multiple correlation coefficients in the multivariate analysis of medical statistics were very high at 0.784. The analyses using pattern recognition methods of these 8 characteristics before endocrine workups were found to be useful to discriminate the patients with CS who needed to undergo surgery. These results indicate that we could screen the patients with CS using routine clinical test parameters, before performing the initial test for CS. In conclusion this efficient and versatile system is clinically very useful, and would improve patients’ QOL.

The present study was carried out to investigate the antioxidant activity and the protective effects of the aqueous leaf extract of Moringa oleifera (MO) on α-radiation-induced toxicity in cardiac and pulmonary tissues in rats. Rats were administered MO (300 mg/kg, oral gavage) for 15 consecutive days and 1 h after the last dose, rats were exposed to 6 Gy α-radiation. Irradiation toxicity was manifested biochemically by an increase in serum triglycerides, total cholesterol and low density lipoprotein-cholesterol, creatine phosphokinase and lactate dehydrogenase activities, elevation of MDA and NO(x) in examined tissues as well as a decrease in serum level of high density lipoprotein-cholesterol and tissue glutathione(GSH) level, catalase(CAT), glutathione peroxidase(GSHPx) and superoxide dismutase(SOD) activities. Marked DNA damage was observed. Pretreatment with MO showed a significant amelioration in the levels of lipid profiles, MDA, NO(x) and DNA damage. The antioxidant enzymes increased significantly along with the levels of GSH. The aqueous extract of MO exhibited strong scavenging effect on 2, 2-diphenyl-2-picryl hydrazyl (DPPH) free radical. Moreover, histopathological examination of heart and lung tissues confirmed the biochemical data. Our results show that pretreatment with MO extract minimize the oxidative stress of α-irradiation indicating its free radical scavenging and potent antioxidant activities.

Aim

Rheumatoid arthritis is a systemic inflammatory disease, which mainly affects joints but can also affect other organs. Ocimum gratissimum L. (Lamiaceae) is a herb, which is reported to have anti-inflammatory activity. So the present investigation was designed to evaluate antiarthritic potential of O. gratissimum in Collagen induced arthritis (CIA) in laboratory animals.

Materials and methods

Fresh leaves were extracted using 95% ethanol by maceration process. The extracts were tested against collagen induced female Sprague-Dawley rats. Arthritis assessment was carried out on the basis of parameters including arthritic score, body weight and paw volume. On day 41, animals were evaluated for biochemical parameter, radiological parameter and histological parameters.

Results

Treatment with 500 mg/kg of EEOG significantly reduced arthritic score, paw volume and almost restored body weight of arthritic animals compared to control animals. Meanwhile, the treatment significantly attenuated biochemical, radiological and histopathological alteration induced by CIA.

Conclusion

EEOG can able to nullify most of the ill effects produced by CIA in rats. However, further studies are needed to carry out identification, isolation of active fractions of EEOG to unravel the mechanism of drug.

Cancer is a group of disease characterized by uncontrolled cell divisions leading to abnormal growth of the tissue. Worldwide, breast cancer is the second most common type of cancer after lung cancer. Estrogen and progesterone bind to the receptors and may work with growth factors to cause cancer cell growth and proliferation. Estrogen receptor alpha (ERα) is essential for mammary gland development and also plays a central role in breast cancer development by mediating estrogen induced cell proliferation. Multidisciplinary scientific investigations are making best efforts to combat this disease, but the perfect cure is yet to be achieved. The side effects of the available drugs make the need for the necessity of new improved drugs. Cyanobacterial resource offers a great scope for discovery of new drugs for breast cancer. Cyanobacterial novel bioactive compounds with unique biological activities may be useful in finding the potential drugs with greater efficacy, specificity for the treatment of human diseases. Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Nowadays, molecular docking approaches are routinely used in modern drug design to understand drug–receptor interaction. Computational techniques can strongly support and help the design of novel, more potent inhibitors by revealing the mechanism of drug-receptor interaction. Hence, the present study is interested to evaluate the interaction of the selected ligands with the breast cancer target receptor. From the study it is concluded that Cryptophycin F, a bioactive compound produced by the Nostoc is a promising potential drug for breast cancer.

Lambda cyhalothrin (LTC) is a synthetic pyrethroid insecticide, widely used to control insect pests in agriculture, public health, and homes and gardens. In the present study, an attempt has been made to study the effect of lambda cyhalothrin on biochemical, hematological parameters and ameliorating effects of palm dates (Phoenix dactylifera) in male wistar rat. Adult male Wistar rats were divided into four different groups. Group I served as control; group II received lambda cyhalothrin at a dose of 8 mg/kg (1/10 LD50) dissolved in water for 21 days orally; group III received P. dactylifera (200 mg/kg BW for 21 days) orally; group IV P. dactylifera alone treated. LTC-induced liver toxicity was measured by the increased activities of serum hepatic marker enzymes like aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, along with increased elevation of lipid peroxidation and reduction in the levels of enzymic and non-enzymic antioxidants levels. Lambda cyhalothrin exposure leads to adverse effects on hematological parameters including erythrocyte (RBCs) and leukocyte (WBCs) counts, hemoglobin concentration (Hb), hematocrit (Hct) and blood indices (MCV and MCH). However, treatment with P. dactylifera normalized the levels of hepatic markers, antioxidant and non-enzymic antioxidant, lipid peroxidation products and all the hematological parameters. These findings highlight the efficacy of P. dactylifera as protective effects against lambda cyhalothrin induced toxicity.

Aim of the study

Cassia auriculata L. (Caesalpiniaceae) is a herb, used as a traditional Indian medicine for inflammation and rheumatism and it is reported to have anti-inflammatory and analgesic activity. In view of its potent anti-inflammatory activity, the present study was designed to evaluate its anti-arthritic activity and to identify the phytoconstituents responsible for the proposed activity.

Material and methods

Anti-arthritic activity of ethyl acetate fraction of Cassia auriculata leaves (EACA) was evaluated using Freund's complete adjuvants (FCA) induced arthritic models in wistar rats. Arthritic assessment was carried out on basis of parameters including paw oedema, motor incordination and nociceptive threshold. At the end of study period, animals were sacrificed and various biochemical, oxidative stress, haematological, radiological and histological parameters were evaluated. The ethyl acetate fraction of Cassia auriculata leaves (EACA) was subjected to qualitative and quantitative phytochemical investigation along with HPTLC analysis using standard biomarker quercetin and gallic acid.

Results

Administration of EACA significantly attenuated the behavioural, biochemical, haematological, radiological alteration induced by the FCA in dose dependent manner. Tibiotarsal joint was extracted for histopathology. The overall results indicate that EACA exerts potent protective effect against FCA induced arthritic rats which is due to its major phytoconstituents quercetin and gallic acid.

Conclusion

From our study we can come to a conclusion that the quercetin and gallic acid present in EACA possess promising ant-arthritic activity by modulating bone erosion which may be attributed to its anti-inflammatory and analgesic activity.