Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer's disease, Parkinson's disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats (n = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.

Abstract. Gynaecological malignancies contribute significantly to cancer burden and have a higher rate of mortality and morbidity. The aim of this retrospective study was to determine the pattern of gynaecological malignancies identified between January, 2000 and December, 2011, at the Centre for Nuclear Medicine and Radiotherapy (CENAR). At CENAR 5,072 female patients were registered with different malignancies, of which 632 cases were gynaecological malignancies. Ovarian cancer (47%) was the most common gynaecological malignancy, followed by cervical cancer (29%), uterine cancer (14%), vulvar and vaginal cancer (6%), and gestational trophoblastic neoplasm (4%). Of the ovarian cancer cases, 72.5% had epithelial while 26.5% had non-epithelial cancer. Squamous cell carcinoma was 75.9% in cervix and 87.8% in vulva and vagina while endometrial carcinoma (75.9%) was more frequent in uterus. For gestational trophoblastic neoplasm, 69.2% of patients had choriocarcinoma. Ovarian cancer was the most common type for the age range of 50-59 years. In the case of cervical and gestational trophoblastic neoplasm the majority of patients presented at the ages of 40-49 and 30-39 years while uterus, vulvar and vaginal tumor presented in the elderly (>60 years). Thus, ovarian cancer is the leading gynecological malignancy in Pakistan.

Cancer invasion involves a series of fundamental heterogeneous steps, with each step being distinct in its type regarding its dependence on various oncogenic pathways. Over the past few years, researchers have been focusing on targeted therapies to treat malignancies relying not only on a single oncogenic pathway, but on multiple pathways. Scientists have recently identified potential targets in the human genome considered earlier as non-functional but the discovery of their potential role in gene regulation has put new insights to cancer diagnosis, prognosis and therapeutics. Non coding RNAs (ncRNAs) have been identified as the key gene expression regulators. Long non-coding RNA (lncRNAs) reveal diverse gene expression profiles in benign and metastatic tumours. Improved clinical research may lead to better knowledge of their biogenesis and mechanism and eventually be used as diagnostic biomarkers and therapeutic agents. Small non coding RNAs or micro RNA (miRNA) are capable of reprogramming multiple oncogenic cascades and, thus, can be used as target agents. This review is aimed to give a perspective of non coding transcription in cancer metastasis with an eye on rising clinical relevance of non coding RNAs and their mechanism of action focusing on potential therapeutics for cancer pathogenesis.

Nanomedicines are applied as alternative treatments for anticancer agents. For the treatment of cancer, due to the small size in nanometers (nm), specific site targeting can be achieved with the use of nanomedicines, increasing their bioavailability and conferring fewer toxic side effects. Additionally, the use of minute amounts of drugs can lead to cost savings. In addition, nanotechnology is effectively applied in the preparation of such drugs as they are in nm sizes, considered one of the earliest cutoff values for the production of products utilized in nanotechnology. Early concepts described gold nanoshells as one of the successful therapies for cancer and associated diseases where the benefits of nanomedicine include effective active or passive targeting. Common medicines are degraded at a higher rate, whereas the degradation of macromolecules is time-consuming. All of the discussed properties are responsible for executing the physiological behaviors occurring at the following scale, depending on the geometry. Finally, large nanomaterials based on organic, lipid, inorganic, protein, and synthetic polymers have also been utilized to develop novel cancer cures.

Various circulating biochemical markers are indicators of pathological state in leukemia and its subtypes. Increased oxidative stress and decreased antioxidant factors portray clear image associated with malignancies during subtypes of leukemia. In this research work we investigated the inter-relationship among the subtypes of leukemia with circulating biochemical markers and oxidative stress in the Pakistani population. This research work was conducted on a total number of 70 subjects in which 20 were control participants and 50 were suffering from leukemia and divided into two subtypes (ALL and AML). Various circulating biomarkers were investigated including hematological, hepatic and renal profiles as well as oxidative stress markers, electrolytes and vitamins C and E. Results show that vitamin E was found to be decreased in diseased sub-types (P < 0.05). Malondialdehyde (MDA) levels were very high in disease sub-types (ALL-B = 8.69 ± 1.59; ALL-T = 8.78 ± 0.97; AML = 8.50 ± 1.29) compared to controls (1.22 ± 0.10; P < 0.05) while the levels of antioxidants [superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), catalase (CAT)], platelets, as well as electrolytes (Ca and Mg) were reduced in patients suffering from leukemia (sub-types). Enhanced levels of oxidative stress (MDA) and decreased levels of enzymatic and non-enzymatic antioxidants reflect the pathological state and impaired cell control in patients suffering from leukemia (subtypes) and show a strong correlation with oxidative stress, indicating that patients' biological systems are under oxidative stress.

BackgroundChronic kidney disease (CKD) is a group of heterogeneous abnormalities affecting the function and structure of the kidney and mostly further proceeds to cardiovascular damage prior to end stage renal disease (ESRD). The oxidative insult and inflammatory mediators have some undefined role in CKD and cardiovascular complications. It is therefore, aimed at to pin point the predictive factors in the development of cardiovascular disorder in patients with chronic kidney disease.MethodsFifty patients of CKD experiencing cardiovascular distress and twenty normal individuals having same age and sex acted as control during these observations. Blood samples (Each 5 ml) were drawn and subjected to centrifugation for 10–15 minutes to separate the serum at 4000-5000rpm. The levels of MDA, GSH, SOD, CAT, VIT C, VIT E, IL-1, TNF-alpha, nitric oxide (NO) and advanced oxidation protein products (AOPPs) were estimated and analyzed.ResultsThe nitric oxide levels in the CKD patients decreased significantly (13.26±1.25 ng/ml) compared to controls (42.15±5.26 ng/ml). The serum vitamin E and C levels in these patients recorded 2.15±0.25 μg/ml and 0.97±0.09 μg/ml respectively as against their assigned controls which read 6.35±1.22 μg/ml and 3.29±0.25 μg/ml. Furthermore, a significantly higher level of Malondialdehyde (MDA) as1.25±0.07 nmol/ml was observed in CKD patients viz-a-viz relevant control. However, the serum SOD, catalase (CAT) and GSH levels in the same patients registered a significant decline as evident from respective figures 0.07±0.002 μg/dl, 1.22±0.012 μmol/mol, and 3.25±1.05 μg/dl. The control for these was observed as0.99±0.06 μg/dl, 3.19±0.05 μmol/mol, and 8.64±0.03 μg/dL. On the other hand, the IL-1 levels in the CKD patients found quite higher (402.5±18.26 pg/ml). This clearly points to substantial increase in oxidative insult and reduced NO levels leading to the renal and cardiovascular damage.ConclusionObservations support the fact that the decrease in anti-oxidative capacity accompanied by higher inflammatory mediators in CKD is indicative of oxidative stress, consequently leading to CKD progression, in all probability to cardiovascular insult. The outcome reiterates that strategies be designed afresh to contain CKD progression to cardiovascular complications and ESRD. One way could be to focus on early detection of stress related to the disease. It requires analyzing the factors related to stress, such as the one reported here. Linking these factors with the symptoms could be a crucial step forward. And further, the disease could be monitored in a more disciplined manner.

Background: Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). Materials and Methods: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.