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Telomere length (TL) and DNA methylation–based epigenetic clocks are markers of biological age, but the relationship between the two is not fully understood. Here, we used multivariable regression models to evaluate the relationships between leukocyte TL (LTL; measured by qPCR [ n  = 635] or flow FISH [ n  = 144]) and five epigenetic clocks (Hannum, DNAmAge pan-tissue, PhenoAge, SkinBlood, or GrimAge clocks), or their epigenetic age acceleration measures in healthy adults (age 19–61 years). LTL showed statistically significant negative correlations with all clocks (qPCR: r  =  − 0.26 to − 0.32; flow FISH: r  =  − 0.34 to − 0.49; p  < 0.001 for all). Yet, models adjusted for age, sex, and race revealed significant associations between three of five clocks (PhenoAge, GrimAge, and Hannum clocks) and LTL by flow FISH ( p  < 0.01 for all) or qPCR ( p  < 0.001 for all). Significant associations between age acceleration measures for the same three clocks and qPCR or flow FISH TL were also found ( p  < 0.01 for all). Additionally, LTL (by qPCR or flow FISH) showed significant associations with extrinsic epigenetic age acceleration (EEAA: p  < 0.0001 for both), but not intrinsic epigenetic age acceleration (IEAA; p  > 0.05 for both). In conclusion, the relationships between LTL and epigenetic clocks were limited to clocks reflecting phenotypic age. The observed association between LTL and EEAA reflects the ability of both measures to detect immunosenescence. The observed modest correlations between LTL and epigenetic clocks highlight a possible benefit from incorporating both measures in understanding disease etiology and prognosis.

Background and Objectives: Stress can overload adaptive mechanisms, leading to epigenetic effects harmful to health. Research on the reversal of these effects is in its infancy. Early results suggest some meditation techniques have health benefits that grow with repeated practice. This study focused on possible transcriptomic effects of 38 years of twice-daily Transcendental Meditation® (TM®) practice. Materials and Methods: First, using Illumina® BeadChip microarray technology, differences in global gene expression in peripheral blood mononuclear cells (PBMCs) were sought between healthy practitioners and tightly matched controls (n = 12, age 65). Second, these microarray results were verified on a subset of genes using quantitative polymerase chain reaction (qPCR) and were validated using qPCR in larger TM and control groups (n = 45, age 63). Bioinformatics investigation employed Ingenuity® Pathway Analysis (IPA®), DAVID, Genomatix, and R packages. Results: The 200 genes and loci found to meet strict criteria for differential expression in the microarray experiment showed contrasting patterns of expression that distinguished the two groups. Differential expression relating to immune function and energy efficiency were most apparent. In the TM group, relative to the control, all 49 genes associated with inflammation were downregulated, while genes associated with antiviral and antibody components of the defense response were upregulated. The largest expression differences were shown by six genes related to erythrocyte function that appeared to reflect a condition of lower energy efficiency in the control group. Results supporting these gene expression differences were obtained with qPCR-measured expression both in the well-matched microarray groups and in the larger, less well-matched groups. Conclusions: These findings are consistent with predictions based on results from earlier randomized trials of meditation and may provide evidence for stress-related molecular mechanisms underlying reductions in anxiety, post-traumatic stress disorder (PTSD), cardiovascular disease (CVD), and other chronic disorders and diseases.

The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3–24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-β signaling, including the androgen/TGF-β inhibitor Prostate transmembrane protein androgen-induced 1 (PMEPA1), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound.

Background In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Methods Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Results Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1 , such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. Conclusions These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis.

Antiphospholipid syndrome (APS) is an autoimmune disorder that causes venous, arterial and small-vessel thrombosis, pregnancy loss, and premature birth. Cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, hemolytic anemia, and cognitive impairment are some of its other clinical symptoms. Antiphospholipid antibodies cause endothelial cells, monocytes, and platelets to become activated, as well as an increase in tissue factor and thromboxane A2. Complement activation might play a key function in pathogenesis.Long-term oral anticoagulation is used to treat thrombosis, and individuals having arterial episodes should be treated quickly. Patients with systemic lupus erythematosus (SLE), as well as those with solely obstetric antiphospholipid syndrome, should get primary thromboprophylaxis. Obstetric care is based on a combination of medical and obstetric high-risk management, as well as aspirin and heparin therapy. Possible supplementary therapy for this condition is hydroxychloroquine. Statins, rituximab, and novel anticoagulant medicines are all potential future treatments for non-pregnant individuals with antiphospholipid syndrome. We aim to review the role of direct-acting oral anticoagulants (DOACs) as thromboprophylactic drugs in the treatment of APS in this article.The treatment of venous thromboembolism has been transformed by a new class of DOACs. These drugs, such as rivaroxaban, function by inhibiting factor Xa directly. Not only do they have known anticoagulant actions, but they also obviate the need for dosage monitoring and modification, in contrast to warfarin.We conducted an exhaustive literature search of PubMed/MEDLINE and Google Scholar Indexes using the keywords “Antiphospholipid syndrome,” “thromboprophylaxis,” and “oral anticoagulants” up to September 2021. We found that DOACs have been shown to be non-inferior to warfarin in a variety of anticoagulation situations in a number of high-powered clinical studies. In many hypercoagulable conditions such as APS, DOACs are quickly establishing themselves as first-line therapy. This article is focused on comprehensively reviewing the mechanism of action of DOACs, their role as thromboprophylactic drugs, risks and complications of DOACs, and comparing their efficacy with the standard treatment protocol and warfarin.

The slowest step in the process usually involves passage through the stratum corneum. [...]this is the rate limits or controls the permeation. Drugs with very short half-lives * e.g nitroglycerine when administered as transdermal patches, release medicaments at a constant rate for a time period more than obtainable with oral formulations. * Permits self administration * Non-invasive (no need to use needles and injection) * Reduces side effect * Allows removal of drug source in case of toxicity * Very simple and easy to use 1.3 Disadvantages: * The drug should have desirable physicochemical properties for penetration through stratum corneum. Classification: Possible useful polymers for Transdermal devices are (4, 10): a) Natural Polymers: e.g. Cellulose derivatives, Zein, Gelatin, Shellac, Waxes, Proteins, Gums and their derivatives, Natural rubber, Starch etc. b) Synthetic Elastomers: e.g. Polybutadieine, Hydrin rubber, Polysiloxane, Silicone rubber, Nitrile, Acrylonitrile, Butyl rubber, Styrenebutadieine rubber, Neoprene etc. c) Synthetic Polymers: e.g.Polyvinylalcohol, Polyvinylchloride, Polyethylene, Polypropylene, Epoxy, Polyacrylate, Polyamide, Polyurea, Polyvinylpyrrolidone etc. d) HPMC: Since it is in intimate contact with the drug and excipients, it should be chemically inert. 1.6Types of TDDS:

[...]if pregnancy has an effect to lower the IOP, more research needs to be done to use the reasons responsible for this in the treatment of glaucoma. [...]it is showing statistical significance between first and third trimesters in pregnancy (P < 0.001) (Table 1). Various underlying mechanisms[3] propose to explain the cause of decrease in IOP during pregnancy, namely, an increase in uveoscleral outflow as a result of hormone levels modification, a decrease in systemic vascular resistance, decrease in episcleral venous pressure, increased tissue elasticity, reduction in the aqueous humor production, and decreased corneoscleral rigidity. Hormone replacement therapy with estrogen and progesterone in post-menopausal women was found to be associated with reduced risk of glaucoma.

The drug is released slowly at the desired rate, but the system is floating on gastric content and increases gastric residence and increases changes in plasma concentration. [...]it also decreases chances of striking and dose dumping. The process of microspheres formation begins the formed polymerize globules start to stick and form the agglomerates. [...]the process variables are critical as they control the kinetic of the formed particles since there is no defined state of equilibrium attainment. Spray drying is the most widely used industrial process involving particle formation and drying. [...]spray drying is an ideal process where the end product must comply with precise quality standards regarding particle size distribution, residual moisture content, bulk density, and particle shape. (12) APPLICATIONS OF MICROSPHERES Medical applications: * Release of proteins, hormones and peptides over extended period of time. * Gene treatment with DNA plasmids and also release of insulin. * Vaccine release for treatment of disease like hepatitis, influenza, pertussis, ricin, toxiod, diphtheria, birth control. * Passive targeting of leaky tumour vessels, active targeting of tumour cells, antigens, by intraarterial/intravenous application. * Tumour targeting with doxorubicin and also treatment of laishmaniasis. * Magnetic microspheres can be used for stem cell withdrawal and bone marrow purging. * Used in separation of antibodies, cell division and toxin withdrawal and bone marrow by attraction chromatography. * Used for various diagnostic tests for communicable diseases like bacterial, viral, and fungal. * Radioactive microsphere's application. * It can be used for radio embolisation of liver and spleen tumours. * Use for radiosynvectomy of arthritis joint, local radiotherapy, interactivity treatment.