With the discovery by Calghatgi (2013) that three common antibiotics (Abs) increased mitochondrial reactive oxygen (ROS) and lipid peroxide (LP) and depleted their natural absorbant glutathione led me to investigate further the potential impacts of these genotoxic substances on carcinogenesis. The range of impacts on mitochondria and cellular DNA varied by antibiotic to those consistent with known prior contributions to carcinogenesis. Specific cancers probably increased by these changes were HCC, RCC (KCC), CRC, cancer of the esophagus. Tumor suppressor gene mutations resulting from LP were noteworthy in this regard and mutations induced in CRC were consistent with those found in carcinogenesis of CRC. In addition depression of short chain fatty acids in microbiomes were found which depress the immune system increasing risk of all cancers. Many cancers were increased according to epidemiological studies linking Abs with elevated odds ratios, with one concern in particular, fatal breast cancer. The impact of loss of functionality of the mitochondria was also linked to depression of the citric acid cycle and therefore ATP which deflected metabolism to glycolysis, the Warburg mechanism also increasing risk of all cancers, favoured by cancer cells. In conclusion, some portion of many cancer types are probably increased in likelihood by number, type and frequency of Abs treatment and chronic residue exposure which varies from individual to individual. This led me to propose a three pronged carcinogenesis mechanism for Abs. 1. Cancer critical mutations 2. Immune depression 3. loss of mitochondrial functionality leading to Warburg effects. Damage to mitochondria were also noted by common pesticides tested in China and cancer associations were also found for many pesticides supporting a similar contributory etiology. Heart health concerns were raised by these findings because of the myriad mitochondria in the heart and because of long term reliability needs. Studies suggesting hearts were affected by Abs and pesticide exposure were presented. Because of their geographical ubiquitousness and the huge range of diseases associated with mitochondrial dysfunction, antibiotics and pesticides and bacteriocidal biocides are of concern for biodiversity and life in general. I propose research steps to evaluate Abs safety and suggest directions for further research and make suggestions on ways to ameliorate Abs toxicity.
Environmental electromagnetic fields are nowadays available in all environments today. These areas affect the biological system. Controlled interactions with elecrtomagnetic fields can have positive effects when unrestricted interactions have negative effects. Uncontrolled exposure to low-frequency electromagnetic fields can cause adverse effects such as signal transduction in cells and tissues, cell membrane structure, ion channels, molecular interactions, DNA damage. But contrary to controlled exposure, it positively affects tissues. The most obvious example of this is seen in the bone and cartilaginous tissue. Repairing fractures and damage in bone and cartilage. This has been shown in many studies. Below is a summary of the relevant information.
Aim and objectives: The primary aim was to measure the sperm DNA damage and to study the magnitude of sperm DNA damage. Secondary objective was to study the effect of sperm DNA fragmentation on Day 5 Blastocyst expansion (graded 1-5).
Results: There is an increase in sperm DNA fragmentation with an increase in age. Increased sperm DNA fragmentation is also associated with abnormal motility and morphology in semen samples. However, there is no reduction in expansion or grade of blastocyst.
Conclusion: Sperm DNA fragmentation testing is a useful investigation in unexplained infertility. However, Sperm DNA fragmentation has no significant association with Day 5 embryo grade in ICSI cycles.
Thesis work of Fellowship in Reproductive Medicine student: Dr. Ramya Harish
Isocitrate dehydrogenase (IDH) mutations are a common event in secondary glioblastoma multiforme and lower-grade adult infiltrative astrocytomas and independently confer a better prognosis [1,2]. These are highly conserved mutations during glioma progression and thus also a useful diagnostic marker amenable to modern molecular sequencing methods. These mutations can even be detected in sites distant from the primary tumour. We use an illustrative case of a patient with radiologically suspected recurrent astrocytoma and negative histology, but positive IDH-mutated tumour DNA detected within CSF. Our results demonstrated the usefulness of liquid biopsy for recurrent glioma within the context of equivocal or negative histopathological results, whilst also showing the ability to detect a de-novo IDH-2 mutation not present in the previous resection. Building on this ‘proof-of-concept’ result, we also take the opportunity to briefly review the current literature describing the various liquid biopsy substrates available to diagnose infiltrative gliomas, namely the study of circulating tumour DNA, circulating tumour cells, and extracellular vesicles. We outline the current challenges and prospects of liquid biopsies in these tumours and suggest that more studies are required to overcome these challenges and harness the potential benefits of liquid biopsies in guiding our management of gliomas
In the current study, combinatorial therapeutic approaches to DNA/RNA of human cancer cells and Benzylpenicillin (Penicillin G), Fluoxetine Hydrochloride (Prozac and Sarafem), Propofol (Diprivan), Acetylsalicylic Acid (ASA) (Aspirin), Naproxen Sodium (Aleve and Naprosyn) and Dextromethamphetamine nanocapsules with surface conjugated DNA/RNA of human cancer cells to targeted Nano drugs for enhanced anti-cancer efficacy and targeted cancer therapy using Nano drugs delivery systems were investigated.
Varicella zoster virus (VZV), a double-stranded DNA virus, is a highly contagious human neurotropic virus that belongs to the alpha group of herpes viruses [1-4]. Primary VZV infection (chickenpox) occurs in childhood then the virus becomes latent in the nerve ganglia [1,5-7]. Reactivation of the virus may occur decades later and cause herpes zoster (HZ) which is manifested by a typical painful skin eruption that has characteristic dermatomal distribution [1,5]. Reactivation of VZV is usually predisposed to: old age; comorbid medical conditions such as diabetes mellitus, chronic obstructive airway disease, and end-stage renal disease; and immunosuppression due to malignancy, autoimmune disorders, immunosuppressive therapies, trauma, cytotoxic chemotherapy, hematopoietic stem cell transplantation (HSCT), and solid organ transplantation (SOT) [1,5-7].
Background: Pulmonary fibrosis is a clinical problem with an enigmatic etiology with no effective therapy. Current therapies for lung fibrosis are ineffective for progression of lung fibrosis and preventing respiratory failure.
Objectives: The aim of this study is to explore the expression of Desmin, α-smooth muscle actin (α-SMA) and the telomerase subunit: human telomerase reverse transcriptase (h-TERT) in a spectrum of lung tissue samples consist of lung fibrosis, lung cancer, and healthy controls.
Materials and Methods: The expression of Desmin, α-SMA and hTERT were studied in samples of 15 pulmonary fibrosis samples, 16 samples of lung cancer and 14 healthy controls investigated. We evaluated Desmin, α-SMA as well as the expression of components of telomerase (TERT), by methods: RNA Extraction and cDNA synthesis, Real-Time quantitative PCR, Immunohistochemistry, all prepared from lung tissue paraffin blocked.
Results: α-SMA marker detected 1(8.3%) of healthy control and 11(91.7%) of lung fibrosis samples. The difference between groups was significant (p<0.001). Also the difference between healthy control 1(6.7%) and lung cancer 14 (93.3%) for α-SMA marker was a significant (P<0.001). It was a significant difference between healthy control and lung cancer for TERT expression (P=.005). TERT was not positive in any sample of neither healthy control nor lung fibrosis. For TERT, it was a significant difference between lung fibrosis and lung cancer by Fisher’s Exact Test (P=.004). Expression of TERT and α-SMA between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was not statistically significant (P=.700, P=0758), respectively.
Conclusions: We recommend more investigation to regard α-SMA, Desmin in patients with lung fibrosis and follow them for possible cancer risk. Also, more study is needed to regard TERT as a marker in lung cancer. Assessment of these markers may have future implication to explain the same way of pathogenesis and carcinogenesis of fibrosis and cancer and for prevention or treatment
Mark Taubert, Lorenz Weidhase, Sirak Petros and Henrik Rueffert*
Published on: 17th October, 2018
A 64-year-old woman was referred to our hospital due to progressive dypnoea for the past week, combined with fever and type 1 respiratory failure. White blood cell count and procalcitonin level were normal. The Chest X-ray showed bilateral disseminated pulmonary infiltrates. Within the next 24 hours the patient developed a severe ARDS. A first diagnostic work-up for typical and atypical pathogens as well as serological tests for CMV, RSV, HIV and HSV were negative. Analysis of a second bronchoalveolar lavage fluid revealed Pneumocystis jiroveci DNA. The patient was successfully treated with trimethoprim-sulfamethoxazole and off label use with caspofungin. The cause of the infection was a six week treatment with dexamethasone. The patient developed a toxic epidermal necrolysis during further course, but completely recovered.
Pneumonia with Pneumocystis jirovecii must also be taken into account in non-HIV patients, whenever there are any indications that cellular immunity may be depressed.
Many pathologic disease can be considered as related to an Endogenous toxicological moves and in time dependent way (kinetics and dynamic of the process). In this work starting from the analysis of relevant literature involved with different disease and related to the endogenous local micro- environment some global conclusion useful as new tools for innovative pharmacological strategies will be submitted to the researcher. Physiology, pathology concept linked to the endogenous toxicological local micro-environment status as new research instruments. The same carcinogenesis process can be related also to endogenous agents that may have a major contribution in spontaneously process. (Reactive oxygen species (ROS), which are involved in multiple cellular processes by physiologically transporting signal as a second messenger or pathologically oxidizing DNA, lipids, and proteins).
Ameloblastoma is a benign odontogenic tumour that may have aggressive biological behavior with local recurrence and metastasis after the surgical resection. We report a case of cytology of recurrent ameloblastoma. The first tumour was diagnosed in the left mandible in 57-yers-old woman thirteen years ago. The patient was operated on, the tumour was enucleated, pathohistological diagnosis of ameloblastoma was put and DNA analysis by flow cytometry of the tumour was performed. DNA analysis showed that the tumour was diploid but proliferative. Two years after the operation, a new tumour appeared on the scar. Fine needle aspiration cytology with ultrasound guidance of the tumour was performed; cytological diagnosis of recurrent ameloblastoma was put and confirmed by pathohistology. Until now the patient is well without any new recurrent ameloblastoma.
Mitomycin-C, first found its way into ophthalmic use in 1969, in Japan, where recurrent pterygia were successfully treated with the drug which is an antineoplastic / antibiotic agent isolated from the soil bacterium Streptomyces caespitosus . It is an anti-metabolite with anti-proliferative effect on cells showing the highest rate of mitosis by inhibiting DNA synthesis and interferes with RNA transcription and protein synthesis .CLINICAL USES
In the current study, we have investigated pros and cons controversy on molecular imaging and dynamics of double-standard DNA/RNA of human preserving stem cells-binding Nano molecules with Androgens/Anabolic Steroids (AAS) or Testosterone derivatives through tracking of Helium-4 nucleus (Alpha particle) using synchrotron radiation. In this regard, the enzymatic oxidation of double-standard DNA/RNA of human preserving stem cells-binding Nano molecules by haem peroxidases (or heme peroxidases) such as Horseradish Peroxidase (HPR), Chloroperoxidase (CPO), Lactoperoxidase (LPO) and Lignin Peroxidase (LiP) is an important process from both the synthetic and mechanistic point of view
This review gives a brief introduction to the microarray technology and its experimental design and data analysis and a discussion of recent global progress in research using microarray technology in fish biology and aquaculture. DNA microarrays have been reported to have been used for the analysis of gene expression during various physiological, developmental or cellular processes in fish. During the recent past, investigators have begun to use microarrays on fish to address ecological, evolutionary and environmental questions including the variability of gene expression in natural populations, speciation, ecotype diversity, environmental remediation and host-pathogen interactions. The study suggests that a lot of gene expression studies have been conducted on salmon and zebrafish in Europe and USA. The same may be applied on Indian Major Carps and Catfishes to augment productivity from aquaculture sector.
The sequence-independent, single-primer amplification (SISPA) enables the random amplification of nucleic acids, allowing the detection and genome sequencing of different viral agents. This feature of SISPA method provides evidence for application of it in monitoring the presence of adventitious RNA viruses in cell cultures. We evaluated SISPA method for the detection of a challenge RNA virus representing adventitious agent in cell cultures. Besides, by optimizing the SISPA method in our laboratory, we found false-positive results on negative control lanes in electrophoresis gels. To investigate the sources of contamination, false-positive results of SISPA were cloned into Escherichia coli cells, sequenced, and phylogenetically analyzed. This data revealed that the SISPA method can be used as an adjunct method to confirm the absence of unexpected adventitious RNA viruses in cell cultures. The phylogenetic analysis of SISPA contaminant sequences showed that the false-positive results were caused by nucleic acid amplification of commercial cDNA synthesis kit reagents, probably tracing back to expression plasmids and host ribosomal sequences, used for the production of enzymes. Therefore, laboratories using random amplification methods must be constantly aware of the potentials of such contaminations, yielding false-positive results and background noise in the final NGS reads.
Radiation of different wavelengths can kill living organisms, although, the mechanism of interactions differs depending on their energies. Understanding the interaction of radiation with living cells is important to assess their harmful effects and also to identify their therapeutic potential. Temporally, this interaction can be broadly divided in three stages – physical, chemical and biological. While radiation can affect all the important macromolecules of the cells, particularly important is the damage to its genetic material, the DNA. The consequences of irradiation include- DNA damage, mutation, cross-linkages with other molecules, chromosomal aberrations and DNA repair leading to altered gene expression and/or cell death. Mutations in DNA can lead to heritable changes and is important for the induction of cancer. While some of these effects are through direct interaction of radiation with the target, radiation can interact with the surrounding environment to result in its indirect actions. The effects of radiation depend not only on the total dose but also on the dose rate, LET etc. and also on the cell types. However, action of radiation on organisms is not restricted to interactions with irradiated cells, i.e. target cells alone; it also exerts non-targeted effects on neighboring unexposed cells to produce productive responses; this is known as bystander effect. The bystander effects of ionizing radiations are well documented and contribute largely to the relapse of cancer and secondary tumors after radiotherapy. Irradiation of cells with non-ionizing Ultra-Violet light also exhibits bystander responses, but such responses are very distinct from that produced by ionizing radiations.
Contemporary forensic science hinges on DNA analysis to link an individual to a crime scene. Sources of DNA include bodily fluids, including saliva. Amylase is a primary enzyme in human saliva and thus, if detected, indicates possible presence of human saliva. Amylase paper can be used to map apparent saliva and thus provide a source from which DNA can be extracted and analyzed. In this study, the sensitivity of amylase paper was tested, firstly, using dilutions of an amylase standard and subsequently also tested using fresh human saliva. Three trials total were conducted, the first two using an amylase standard and a third using fresh saliva. The first two trials demonstrated firstly that detection of amylase is dependent on the material upon which amylase is deposited. The third trial demonstrated that amylase levels in human saliva may drop significantly somewhere around 48-72 hours. All trials were consistent in the concentration of amylase that Seratec Amylase Paper will detect.
Pieces of evidence have continued to emerge, demonstrating the extensive efficiency and effectiveness of the DNA database in assisting criminal investigations around the world. Therefore, the present study aimed to determine the awareness level on the prominent role of Forensic DNA Database on Crime Investigation in Nigeria: a case study of Benin City. In conducting this research, a total of 458 questionnaires were distributed around Benin City between the periods of 12th January 2020 to 21st March 2020, with a particular focus on security agents and students. The questionnaire comprised of three main categories: Socio-demographic characteristics, Information about the National Forensic DNA Database, and Information about DNA evidence, and Nigeria Criminal Justice system. For the analysis of data collected; the statistical tool used was also Statistical Package for Social Sciences, version 22 for windows. Responses were compared using chi-square and presented as counts and percentages. In determining the level of awareness, the following responses were obtained. Of the total population: 53.28% had no idea about forensics, 19.21% were uncertain and 27.54% knew about forensics. The same trend was observed with Forensic DNA profiling, 42.14% did not know, 22.27% were uncertain and 35.59% demonstrated good knowledge of Forensic DNA profiling. On the knowledge about the National Forensic DNA Database, 48.47% had no knowledge, 22.27% were uncertain and 29.26% were knowledgeable about it. The result of the present study revealed that the awareness level of the forensic DNA Database was found to be inadequate.
Growing evidence supports the hypothesis that endothelial cell-derived microparticles (MPs) might contribute to the pathogenesis of cardiovascular (CV) disease. Endothelial cell-derived MPs play a pivotal role in the regulation of the endogenous repair system, thrombosis, coagulation, inflammation, immunity and metabolic memory phenomenon. There is evidence that the MPs are secreted actively accompanied to other regulatory molecules. All these actively synthetizing and secreting factors include proteins, adhesion and intercellular signal molecules, peptides, lipids, free DNAs, microRNAs, and even microparticles (MPs) are defined as cellular secretome. The proteomic profile of secretome is under tightly control of genetic and epigenetic mechanisms, which may altered a secretion of the proteins involved into MPs’ organization. Finally, this may contribute the modification of MP’s after their secretion and throughout transfer to the target cells. As a result, communicative ability of endothelial cell-derived MPs may sufficiently worse. Subsequently, cross talk between some components of secretome might modulate delivering cargos of MPs and their regenerative and proliferative capabilities via intercellular signaling networks. The aim of the review is to discuss the effect of various components of secretome on MP-dependent effects on endothelium.
Colon cancer (CC) screening is important for diagnosing early stage for malignancy and therefore potentially reduces mortality from this disease because the cancer could be cured at the early disease stage. Early detection is needed if accurate and cost effective diagnostic methods are available. Mortality from colon cancer is theoretically preventable through screening. The Current screening method, the immunological fecal occult blood test, FOBTi, lacks sensitivity and requires dietary restriction, which impedes compliance. Moreover colonoscopy is invasive and costly, which decreases compliance, and in certain cases could lead to mortality. Compared to the FOBT test, a noninvasive sensitive screen that does not require dietary restriction would be more convenient. Colonoscopy screening is recommended for colorectal cancer (CRC). Although it is a reliable screening method, colonoscopy is an invasive test, often accompanied by abdominal pain, has potential complications and has high cost, which have hampered its application worldwide.
A screening approach that uses the relatively stable and nondegradable microRNA molecules when extracted from either the noninvasive human stool, or the semi-invasive blood samples by available commercial kits and manipulated thereafter, would be more preferable than a transcriptomic messenger (m)RNA-, a mutation DNA-, an epigenetic-or a proteomic-based test. That approach utilizes reverse transcriptase (RT), followed by a modified quantitative real-time polymerase chain reaction (qPCR). To compensate for exosomal miRNAs that would not be measured, a parallel test could be performed on stool or plasma’s total RNAs, and corrections for exosomal loss are made to obtain accurate results. Ultimately, a chip would be developed to facilitate diagnosis, as has been carried out for the quantification of genetically modified organisms (GMOs) in foods. The gold standard to which the miRNA test is compared to is colonoscopy. If laboratory performance criteria are met, a miRNA test in human stool or blood samples based on high throughput automated technologies and quantitative expression measurements currently employed in the diagnostic clinical laboratory, would eventually be advanced to the clinical setting, making a noticeable impact on the prevention of colon cancer.
The normal levels of thyroid hormones (THs; thyroxine, T4 & 3,5,3′-triiodo-L-thyronine, T3) are necessary for the normal development [1-48], particularly the fetal and neonatal cardiac growth and development . The actions of THs are facilitated genomically by thyroid receptors (TRs, α and β) and non-genomically at the plasma membrane, in the cytoplasm and in cellular organelles [4,49-55], by stimulation of Na+, K+, Ca2+ and glucose transport, activation of protein kinase C (PKC), protein kinase A (PKA) and mitogen activated and protein kinase (ERK/MAPK) . In addition, the transport of T4 and T3 in and out of cells is controlled by several classes of transmembrane TH-transporters (THTs) , including members of the organic anion transporter family (OATP), L-type amino acid transporters (LATs), Na+/Taurocholate cotransporting polypeptide (NTCP), and monocarboxylate transporters (MCTs) [4,49,57,58]. Adding additional complexity, the metabolism of T4 and T3 is regulated by 3 selenoenzyme iodothyronine deiodinases (Ds: D1, D2 and D3) [59-61]. On the other hand, the congenital hypothyroidism can cause the following [49,62-64], (1) congenital heart diseases; (2) diastolic hypertension; (3) reduced cardiac output, stroke volume and a narrow pulse pressure; (4) dilatation and overt heart failure; (5) elevation in the systemic vascular resistance [65-68]. Similarly, the chronic hyperthyroidism can cause the following [49,64]: (1) cardiac hypertrophy; (2) increase in the cardiomyocyte (CM) length rather than width; (3) noticeable diminution in systemic vascular resistance; (4) elevation in the cardiac contractility; (5) systolic hypertension; (6) increase in the cardiac output, venous volume return, blood volume and pulse pressure; and (7) reduction in the systemic vascular resistance [49,69]. T3-therapy can induce DNA synthesis and cardiomyocyte proliferation, and improve the cardiac contractility; though, this action is as still unidentified [49,70-74].
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