Isotamarixen - a new antioxidant and prolyl endopeptidase-inhibiting triterpenoid from Tamarix hispida

A new pentacyclic triterpenoid, 3alpha-(3",4"-dihydroxy- trans-cinnamoyloxy)- D-friedoolean-14-en-28-oic acid ( 1) has been isolated along with two known compounds, rhamnocitrin ( 2) and isorhamnetin ( 3) from the aerial parts of Tamarix hispida Willd. Compound 1 was found to be a potent antioxidant. In addition, compounds 1 - 3 showed significant inhibitory activity against prolylendopeptidase (PEP).     

Granulomas in acquired immunodeficiency syndrome‐associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis

Background: Co‐lesional acquired immunodeficiency syndrome‐associated cutaneous Kaposi sarcoma (AIDS‐KS) and Mycobacterium tuberculosis‐associated granulomatous inflammation are undocumented. Method: Retrospective appraisal of skin biopsies with co‐lesional AIDS‐KS and microscopic tuberculosis (TB). Results: Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non‐necrotizing and a combination of necrotizing and non‐necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl‐Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co‐lesional TB in 15/16 biopsies. Co‐lesional AIDS‐KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. Conclusion: Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co‐lesional occurrence of AIDS‐KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB. Ramdial PK, Sing Y, Subrayan S, Calonje E, Aboobaker J, Sydney C, Sookdeo D, Ramburan A, Madiba TE. Granulomas in acquired immunodeficiency syndrome‐associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis.     

Microsatellite analysis of the adenomatous polyposis coli (APC) gene and immunoexpression of beta catenin in nephroblastoma: a study including 83 cases treated with preoperative chemotherapy

AIMS: To determine whether microsatellite mutations of the adenomatous polyposis coli (APC) gene have pathological or prognostic significance in nephroblastomas and to correlate APC alterations with beta catenin immunoexpression. METHODS: One hundred nephroblastomas were analysed, 83 of which received preoperative chemotherapy. Normal and tumour DNA was isolated using standard proteinase K digestion and phenol/chloroform extraction from paraffin wax embedded tissue. Polymerase chain reaction using four APC microsatellite markers-D5S210, D5S299, D5S82, and D5S346-was performed and the products analysed. Immunohistochemistry was performed using the LSAB kit with diaminobenzidine as chromogen. Results were correlated with clinicopathological data using the chi(2) test. RESULTS: Allelic imbalance/loss of heterozygosity was more frequent than microsatellite instability, with 30% of cases showing allelic imbalance/ loss of heterozygosity and 16% showing microsatellite instability. Although there was a significant correlation between the results for individual markers and the clinicopathological data, the overall results do not support a prognostic role for APC in nephroblastoma. Expression of beta catenin was seen in 93% of cases. Staining was predominantly membranous, with epithelium, blastema, and stroma being immunoreactive. Cytoplasmic redistribution was seen in 58% of cases, but no nuclear staining was detected. No significant associations between beta catenin expression and the clinicopathological parameters were found. Kaplan-Meier survival plots showed that patients with loss of membranous staining and pronounced cytoplasmic staining (score, 3) had a significantly shorter survival (p = 0.04; median survival, 5.87 months). CONCLUSION: Microsatellite analysis of APC and immunoexpression of beta catenin did not provide significant pathological or prognostic information in this cohort of nephroblastomas.     

Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa

AIMS: To investigate the incidence of genetic aberrations in the DNA repair genes in a cohort of oesophageal cancers. METHODS: One hundred oesophagectomy samples of squamous cell carcinoma were studied. Normal and tumour DNA were isolated using a standard phenol/chloroform extraction procedure. Six recommended microsatellite loci with high informativity were analysed. The following markers were used: D2S123 (2p), D3S659 (3p), D3S1255 (3p), Bat 25 (4q), Bat 26 (2p), and Bat 40 (1p). The results were analysed using software attached to an automated DNA sequencer. The molecular data were then correlated with clinicopathological parameters. RESULTS: The incidence of microsatellite instability and loss of heterozygosity was very low. There was no significant correlation between the clinicopathological and molecular data. However, D2S123 genetic abnormalities were seen more frequently in both moderately and well differentiated tumours than in poorly differentiated tumours (p = 0.033). Follow up data were available for only 67 of the 100 patients. Fifty patients were alive and 17 patients had died. CONCLUSION: Low frequencies of genetic aberrations in these mismatch repair loci are found in squamous carcinomas of the oesophagus from a high incidence area in South Africa.     

New bioactive diterpene polyesters from Euphorbia decipiens

A reinvestigation with a modified extraction procedure of Euphorbia decipiens resulted in the isolation and structure elucidation of three new myrsinane-type diterpene esters (1-3). The structures of compounds 1-3 were elucidated by spectroscopic data interpretation. Compound 1 showed inhibitory activity against prolyl endopeptidase (PEP), whereas compound 2 exhibited DNA-damaging activity in a mutant yeast bioassay.     

The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline

Recent emerging research on intestinal microbiota and its contribution to the central nervous system during health and disease has attracted significant attention. Age-related intestinal microbiota changes initiate brain aging and age-related neurodegenerative disorders. Aging is one of the critical predisposing risk factors for the development of neurodegenerative diseases. Maintaining a healthy gut microbiota is essential for a healthy body and aging, but dysbiosis could initiate many chronic diseases. Understanding the underlying mechanisms of gut microbiota alterations/dysbiosis will help identify biomarkers for aging-related chronic conditions. This review summarizes recent advances in microbiota-neurodegenerative disease research and will enhance our understanding of gut microbiota dysbiosis and its effects on brain aging.Key Words: brain aging, cognitive decline, dysbiosis, fecal microbiota transplantation, gut-microbiota, neuroinflammation, prebiotics, probiotics     

Microsatellite analysis of the DCC gene in nephroblastomas: pathologic correlations and prognostic implications.

Microsatellite instability has been reported in a wide variety of cancer types. Inactivation or loss of tumour suppressor genes has been shown to result in cell cycle deregulation and neoplastic growth. We conducted a microsatellite study using fluorescent-based DNA technology to determine whether mutations in the microsatellite sequences of the deleted in colorectal cancer (DCC) gene, a tumour suppressor at 18q21.1, have any pathologic correlation or prognostic significance in nephroblastomas. Normal and tumour DNA was isolated from 106 cases of nephroblastoma using the standard proteinase K digestion and phenol-chloroform extraction method from paraffin wax-embedded tissue. Polymerase chain reaction using three microsatellite markers; D18S21, D18S34 and D18S58, for the DCC gene were performed. The polymerase chain reaction products were analysed on the ALF Express Automated DNA sequencer. The results were correlated with age at diagnosis, preoperative chemotherapy, clinicopathological stage, histological classification and patient outcome using chi(2) test. Allelic imbalance/loss of heterozygosity appeared to be a more frequent genetic aberration than microsatellite instability with 20% of cases showing allelic imbalance/loss of heterozygosity and only 9% of cases showing microsatellite instability. Genetic aberrations were more frequent in unfavourable histology tumours compared to favourable histology tumours (P=0.012). All patients with genetic aberrations for more than one DCC marker died independent of histological classification and stage (P=0.016). There was no statistically significant difference when DCC aberrations were compared with age at diagnosis, preoperative chemotherapy and clinicopathological stage. In conclusion, this study has found that multiple aberrations involving the DCC locus may play a role in the progression of nephroblastomas, and hence confer a poorer prognosis.     

Bioactive constituents from Boswellia papyrifera

Phytochemical investigation of the stem bark extract of Boswellia papyrifera afforded two new stilbene glycosides, trans-4',5-dihydroxy-3-methoxystilbene-5-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranoside (1), trans-4',5-dihydroxy-3-methoxystilbene-5-O-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranoside (2), and a new triterpene, 3alpha-acetoxy-27-hydroxylup-20(29)-en-24-oic acid (3), along with five known compounds, 11-keto-beta-boswellic acid (4), beta-elemonic acid (7), 3alpha-acetoxy-11-keto-beta-boswellic acid (8), beta-boswellic acid (9), and beta-sitosterol (10). The stilbene glycosides exhibited significant inhibition of phosphodiesterase I and xanthine oxidase. The triterpenes (3-9) exhibited prolyl endopeptidase inhibitory activities.     

The role of cofilin in age-related neuroinflammation

Aging brain becomes susceptible to neurodegenerative diseases due to the shifting of microglia and astrocyte phenotypes to an active“pro-inflammatory”state,causing chronic low-grade neuroinflammation.Despite the fact that the role of neuroinflammation during aging has been extensively studied in recent years,the underlying causes remain unclear.The identification of relevant proteins and understanding their potential roles in neuroinflammation can help explain their potential of becoming biomarkers in the aging brain and as drug targets for prevention and treatment.This will eventually reduce the chances of developing neurodegenerative diseases and promote healthier lives in the elderly.In this review,we have summarized the morphological and cellular changes in the aging brain,the effects of age-related neuroinflammation,and the potential role of cofilin-1 during neuroinflammation.We also discuss other factors contributing to brain aging and neuroinflammation.