Common Human Diseases Research Articles

Establishment of Down\u2019s syndrome periodontal ligament cells by transfection with SV40T-Ag and hTERT

Down’s syndrome is one of the most common human congenital genetic diseases and affected patients have increased risk of periodontal disease. To examine involvement of the disease with periodontal disease development, we established immortalized periodontal ligament cells obtained from a Down’s syndrome patient by use of SV40T-Ag and hTERT gene transfection. Expressions of SV40T-Ag and hTERT were observed in periodontal ligament cell-derived immortalized cells established from healthy (STPDL) and Down’s syndrome patient (STPDLDS) samples. Primary cultured periodontal ligament cells obtained from a healthy subject (pPDL) had a limited number of population doublings (< 40), while STPDL and STPDLDS cells continued to grow with more than 80 population doublings. Primary cultured periodontal ligament cells obtained from the patient showed a chromosome pattern characteristic of Down’s syndrome with trisomy 21, whereas STPDLDS samples showed a large number of abnormal chromosomes in those results. Gene expression analysis revealed that expression of DSCR-1 in STPDLDS is greater than that in STPDL. These results suggest that the newly established STPDLDS cell line may be a useful tool for study of periodontal disease in Down’s syndrome patients.

A review on antiviral efficacy of Bifidobacterium species

Viral infections like diarrheal infections (Rotavirus diarrhea) and respiratory infections transmitted virus (influenza virus [IFV]) are of the most common diseases in humans. Studies have shown that probiotics are able to decrease the risk or duration of viral infection symptoms. The purpose of this paper is to review the current studies on the efficacy of Bifidobacterium spp on viral infections and to provide insights on their possible antiviral mechanisms. A PubMed, Scopus, and Google Scholar database search was performed up to February 2021 using appropriate search terms The terms ‘probiotic’, ‘bifidobacterium’ and ‘virus’. Altogether, 21 relevant studies were obtained which 8, 4, and 9 studies were related to antiviral efficacy of Bifidobacterium spp on Rotavirus, IFV, and other viruses, respectively. Based on reviewed studies, Bifidobacterium spp may exert their antiviral effects via direct interaction or via stimulation of the immune system. More in vitro, in vivo, and clinical trials are needed to evaluate the antiviral efficacy and mechanisms of Bifidobacterium spp.

Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms.

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

Quercetin and Its Role in Reducing the Expression of Pro-inflammatory Cytokines in Osteoarthritis.

Osteoarthritis is the most common human joint disease in the world. It is also one of the most common skeletal muscle defects, destructive joint changes, and the leading cause of disability and reduced quality of life. Destructive changes in inflammatory joints are associated with a range of biochemical events, including the overproduction of inflammatory cytokines. Cytokines are protein compounds that play an essential role in causing and regulating inflammation. A balance between pro-inflammatory and anti-inflammatory cytokines is crucial in maintaining a stable body. In some inflammatory diseases, including osteoarthritis, the balance between these compounds is disturbed, and the balance shifts to pre-inflammatory cytokines. For this reason, researchers today are trying to find an effective way to reduce inflammation and treat osteoarthritis by using certain compounds. Current treatments for osteoarthritis, including nonsteroidal antiinflammatory drugs, glucocorticoids, and hyaluronic acid, are mainly based on reducing pain and inflammation. However, they have limited effects in controlling symptoms and improving the patient's quality of life. Also, due to the high level of side effects, synthetic drugs have led to the identification of compounds of natural origin to give patients a chance to use painkillers and antiinflammatory drugs with fewer side effects. This review study aimed to present the role of quercetin as a natural compound in reducing the expression of pro-inflammatory cytokines in osteoarthritis. This study also discusses the relationship between inflammation and cartilage destruction and other inflammation-related factors caused by cytokines.

Detection of Borrelia burgdorferi antigens in tissues and plasma during early infection in a mouse model

Borrelia burgdorferi is the causative agent of Lyme borreliosis, which is the most common tick-borne human disease in Europe and North America. Currently, the diagnosis of Lyme borreliosis is based on serological tests allowing indirect detection of anti-Borrelia antibodies produced by patients. Their main drawback is a lack of sensitivity in the early phase of disease and an incapacity to prove an active infection. Direct diagnostic tests are clearly needed. The objectives of this study were to produce tools allowing sensitive detection of potential circulating Borrelia antigens and to evaluate them in a mouse model. We focused on two potential early bacterial makers, the highly variable OspC protein and the conserved protein FlaB. High-affinity monoclonal antibodies were produced and used to establish various immunoassays and western blot detection. A very good limit of detection for OspC as low as 17 pg/mL of sample was achieved with SPIE-IA. In infected mice, we were able to measure OspC in plasma with a mean value of 10 ng/mL at 7 days post-inoculation. This result suggests that OspC could be a good blood marker for diagnosis of Lyme borreliosis and that the tools developed during this study could be very useful.

The Effect of 630 nm Photobiomodulation on the Anti-Inflammatory Effect of Human Gingival Fibroblasts

Periodontal disease is the most common oral chronic inflammatory disease in humans. Recent studies have indicated that red light Photobiomodulation (PBM) could inhibit cell inflammation effectively, but the effect of different doses of PBM on the treatment of inflammation has to be improved. Thus, this study was aimed to investigate the effects of various doses of PBM (630 ± 30 nm, (1) 5 mW/cm2, 1 J/cm2, 200 s; (2) 5 mW/cm2, 3 J/cm2, 600 s; (3) 5 mW/cm2, 9 J/cm2, 1800 s; (4) 5 mW/cm2, 18 J/cm2, 3600 s; (5) 5 mW/cm2,36 J/cm2, 7200 s) on the anti-inflammatory response of human gingival fibroblasts. Our results suggested that PBM (630 ± 30 nm) with doses of 18 J/cm2 and 36 J/cm2 could significantly inhibit the production of inflammatory cytokines such as Prostaglandin E2 (PGE2) and IL-8, presumably due to the fact that a high dose of PBM treatment could reduce intracellular Reactive oxygen species (ROS) in human gingival fibroblasts, thus reducing the expression of COX-2 enzyme. In addition, it was found that treatment with different doses of PBM (630 ± 30 nm) did not result in reduced mitochondrial membrane potential and mitochondrial dysfunction in human gingival fibroblasts. Our study provides a theoretical reference for the selection of PBM parameters and the application of PBM in the clinical treatment of periodontitis.

Linking common human diseases to their phenotypes; development of a resource for human phenomics

BackgroundIn recent years a large volume of clinical genomics data has become available due to rapid advances in sequencing technologies. Efficient exploitation of this genomics data requires linkage to patient phenotype profiles. Current resources providing disease-phenotype associations are not comprehensive, and they often do not have broad coverage of the disease terminologies, particularly ICD-10, which is still the primary terminology used in clinical settings.MethodsWe developed two approaches to gather disease-phenotype associations. First, we used a text mining method that utilizes semantic relations in phenotype ontologies, and applies statistical methods to extract associations between diseases in ICD-10 and phenotype ontology classes from the literature. Second, we developed a semi-automatic way to collect ICD-10–phenotype associations from existing resources containing known relationships.ResultsWe generated four datasets. Two of them are independent datasets linking diseases to their phenotypes based on text mining and semi-automatic strategies. The remaining two datasets are generated from these datasets and cover a subset of ICD-10 classes of common diseases contained in UK Biobank. We extensively validated our text mined and semi-automatically curated datasets by: comparing them against an expert-curated validation dataset containing disease–phenotype associations, measuring their similarity to disease–phenotype associations found in public databases, and assessing how well they could be used to recover gene–disease associations using phenotype similarity.ConclusionWe find that our text mining method can produce phenotype annotations of diseases that are correct but often too general to have significant information content, or too specific to accurately reflect the typical manifestations of the sporadic disease. On the other hand, the datasets generated from integrating multiple knowledgebases are more complete (i.e., cover more of the required phenotype annotations for a given disease). We make all data freely available at https://doi.org/10.5281/zenodo.4726713.

Black Garlic and Its Bioactive Compounds on Human Health Diseases: A Review.

Black garlic (BG) is a form of aged garlic obtained from raw garlic (Allium sativum) via Millard reaction under high temperature (60–90 °C) and humidity (70–90%) for a period of time. Several studies reported higher contents of water-soluble antioxidants compounds (S-allyl cysteine, S-allyl-mercapto cysteine), 5-hydroxymethylfurfural, organosulfur compounds, polyphenol, volatile compounds, and products of other Millard reactions compared to fresh garlic after the thermal processing. Recent studies have demonstrated that BG and its bioactive compounds possess a wide range of biological activities and pharmacological properties that preserve and show better efficacy in preventing different types of diseases. Most of these benefits can be attributed to its anti-oxidation, anti-inflammation, anti-obesity, hepatoprotection, hypolipidemia, anti-cancer, anti-allergy, immunomodulation, nephroprotection, cardiovascular protection, and neuroprotection. Substantial studies have been conducted on BG and its components against different common human diseases in the last few decades. Still, a lot of research is ongoing to find out the therapeutic effects of BG. Thus, in this review, we summarized the pre-clinical and clinical studies of BG and its bioactive compounds on human health along with diverse bioactivity, a related mode of action, and also future challenges.

A mutation in desmin makes skeletal muscle less vulnerable to acute muscle damage after eccentric loading in rats.

Desminopathy is the most common intermediate filament disease in humans. The most frequent mutation causing desminopathy in patients is a R350P DES missense mutation. We have developed a rat model with an analogous mutation in R349P Des. To investigate the role of R349P Des in mechanical loading, we stimulated the sciatic nerve of wild‐type littermates (WT) (n = 6) and animals carrying the mutation (MUT) (n = 6) causing a lengthening contraction of the dorsi flexor muscles. MUT animals showed signs of ongoing regeneration at baseline as indicated by a higher number of central nuclei (genotype: P < .0001). While stimulation did not impact central nuclei, we found an increased number of IgG positive fibers (membrane damage indicator) after eccentric contractions with both genotypes (stimulation: P < .01). Interestingly, WT animals displayed a more pronounced increase in IgG positive fibers with stimulation compared to MUT (interaction: P < .05). In addition to altered histology, molecular signaling on the protein level differed between WT and MUT. The membrane repair protein dysferlin decreased with eccentric loading in WT but increased in MUT (interaction: P < .05). The autophagic substrate p62 was increased in both genotypes with loading (stimulation: P < .05) but tended to be more elevated in WT (interaction: P = .05). Caspase 3 levels, a central regulator of apoptotic cell death, was increased with stimulation in both genotypes (stimulation: P < .01) but more so in WT animals (interaction: P < .0001). Overall, our data indicate that R349P Des rats have a lower susceptibility to structural muscle damage of the cytoskeleton and sarcolemma with acute eccentric loading.

Dengue Infection: Frequently Asked Questions by People in the Province of Aklan, Philippines

Dengue virus is the most common mosquito borne viral disease in humans, and poses a major challenge to global public health services. Infection can be caused by any of the 4 DENV serotypes, transmitted by female Aedes aegypti mosquitoes. Presenting features may vary from a mild self-limiting febrile illness to life-threatening symptoms of bleeding, organ impairment, and plasma leakage leading to shock. Early diagnosis and monitoring are critical to reduce mortality, especially in the context of the COVID-19 pandemic. Laboratory tests, such as the serological detection of either antigen or antibodies are useful in the diagnosis. Currently, although a vaccine for DENV is available, it remains a challenge to develop an effective vaccine against 4 discrete serotypes and antiviral drugs effective in reducing morbidity or improving disease outcome.

Interactions of Mitochondrial Transcription Factor A with DNA Damage: Mechanistic Insights and Functional Implications.

Mitochondria have a plethora of functions in eukaryotic cells, including cell signaling, programmed cell death, protein cofactor synthesis, and various aspects of metabolism. The organelles carry their own genomic DNA, which encodes transfer and ribosomal RNAs and crucial protein subunits in the oxidative phosphorylation system. Mitochondria are vital for cellular and organismal functions, and alterations of mitochondrial DNA (mtDNA) have been linked to mitochondrial disorders and common human diseases. As such, how the cell maintains the integrity of the mitochondrial genome is an important area of study. Interactions of mitochondrial proteins with mtDNA damage are critically important for repairing, regulating, and signaling mtDNA damage. Mitochondrial transcription factor A (TFAM) is a key player in mtDNA transcription, packaging, and maintenance. Due to the extensive contact of TFAM with mtDNA, it is likely to encounter many types of mtDNA damage and secondary structures. This review summarizes recent research on the interaction of human TFAM with different forms of non-canonical DNA structures and discusses the implications on mtDNA repair and packaging.

SCMFMDA: Predicting microRNA-disease associations based on similarity constrained matrix factorization.

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.

Predicting Type 2 Diabetes Using Logistic Regression and Machine Learning Approaches

Diabetes mellitus is one of the most common human diseases worldwide and may cause several health-related complications. It is responsible for considerable morbidity, mortality, and economic loss. A timely diagnosis and prediction of this disease could provide patients with an opportunity to take the appropriate preventive and treatment strategies. To improve the understanding of risk factors, we predict type 2 diabetes for Pima Indian women utilizing a logistic regression model and decision tree—a machine learning algorithm. Our analysis finds five main predictors of type 2 diabetes: glucose, pregnancy, body mass index (BMI), diabetes pedigree function, and age. We further explore a classification tree to complement and validate our analysis. The six-fold classification tree indicates glucose, BMI, and age are important factors, while the ten-node tree implies glucose, BMI, pregnancy, diabetes pedigree function, and age as the significant predictors. Our preferred specification yields a prediction accuracy of 78.26% and a cross-validation error rate of 21.74%. We argue that our model can be applied to make a reasonable prediction of type 2 diabetes, and could potentially be used to complement existing preventive measures to curb the incidence of diabetes and reduce associated costs.

Epidemiological approach to an outbreak of gastroenteritis in Ondo State, South West, Nigeria

Background: Acute gastroenteritis, a very common disease in humans affecting both children and adults, remains a major public health concern worldwide. Several groups of viruses have been reported as the causative agents of acute gastroenteritis. An outbreak of acute gastroenteritis with a high fatality rate was reported in Ondo State, Southwest, Nigeria, in September 2020. Methods: To provide a descriptive epidemiology of the outbreak, a field investigation was carried out in affected communities in September 2020. Results: Four Local Government Areas (LGA) were affected, with Odigbo LGA having the highest attack rate of 14.9 per 100,000 population. The epidemic curve was propagated in nature. 50 cases were reported with 21 deaths (42%). The outbreak primarily affected 15-year-olds (94%, n=47) and more males (58%, n=29). Conclusion: Poor sanitation, food, and water hygiene conditions in communities of the LGA visited were observed. The spread of the outbreak was probably facilitated by water sellers.

Use of Box–Behnken design for optimization of compounded medication: acyclovir capsules report

Campus compounding pharmacies play an important role in public health. Herpes simplex is one of the most common viral diseases in humans, which generates a great demand for acyclovir capsules in compounding pharmacy. It is well known that the formulation's components influence the effectiveness of the drug. The objective of this study is to show the applicability of Box-Behnken design in optimization of a compounded formulation and to evaluate the effect of excipients on dissolution and drug content in acyclovir 200 mg capsules produced at UFF´s University Pharmacy (FAU). The formulations were prepared and evaluated for average weight test, uniformity of dosage units and in vitro dissolution, while meeting pharmacopoeial specifications. A statistical analysis showed that sodium starch glycolate, Aerosil®, influences drug content and dissolution results. Magnesium stearate shows no influence on the dissolution at different concentrations but influences the assay results. A numerical optimization was applied to adjust the formulation variables based on the foresaid responses, accomplishing the best formulation that will be prepared and dispensed at FAU upon medical prescription.

Pharmacognostical and Physico-chemical Evaluation of Ativishadi Churna – An Ayurvedic Formulation

Ativishadi churna is a traditional classical formulation pioneered by the science of Ayurveda. The very first reference regarding the formulation was documented in the Charka Samhita under title Ativishadi Yoga. The main indication of this formulation is to cure diarrhoea due to pitta dosha vitiation. It contains an equal part of powdered and dried Ativisha roots, Kutaj bark and Indrayava (dried Kutaj seeds). The polyherbal formulations comprise a wide range of bioactive compounds and the standardization of such formulations is a great concern these days. Hence, the present study evolves around standardizing Ativishadi Churna, for this purpose physicochemical parameters were performed of individual drugs by keeping the values of API as a standard. A complete pharmacognostic profile of ingredients has been validated to authenticate plant materials and to confirm the absence of any adulterants or impurities in the formulation. The preliminary phytochemical tests, Pharmacognostic and phytochemical standardization of the formulation were performed as a part of an SOP development. The formulation besides has been proven to possess antimicrobial properties against pathogens responsible for common infectious diseases in humans. The recent concern lies in the fact that some traditional medicines have been claimed to possess heavy metals. For this purpose, the heavy metal content has also been determined which shows that the formulation is devoid of heavy metals that may cause toxicity. The pharmacognostic and phytochemical study of this formulation would be very important for establishing standards in the future.

Emerging Role of Epigenetics in Explaining Relationship of Periodontitis and Cardiovascular Diseases.

Cardiovascular diseases such as ischemic heart diseases or stroke are among the leading cause of deaths globally, and evidence suggests that these diseases are modulated by a multifactorial and complex interplay of genetic, environmental, and lifestyle factors. Genetic predisposition and chronic exposure to modifiable risk factors have been explored to be involved in the pathophysiology of CVD. Environmental factors contribute to an individual’s propensity to develop major cardiovascular risk factors through epigenetic modifications of DNA and histones via miRNA regulation of protein translation that are types of epigenetic mechanisms and participate in disease development. Periodontal disease (PD) is one of the most common oral diseases in humans that is characterized by low-grade inflammation and has been shown to increase the risk of CVDs. Risk factors involved in PD and CVD are determined both genetically and behaviorally. Periodontal diseases such as chronic inflammation promote DNA methylation. Epigenetic modifications involved in the initiation and progression of atherosclerosis play an essential role in plaque development and vulnerability. Epigenetics has opened a new world to understand and manage human diseases, including CVDs and periodontal diseases. Genetic medicine has started a new era of epigenetics to overcome human diseases with various new methodology. Epigenetic profiling may aid in better diagnosis and stratification of patients showing potential predisposed states for disease. A better understanding of the exact regulatory mechanisms of epigenetic pathways driving inflammation is slowly emerging and will aid in developing novel tools for the treatment of disease.

Nutritional, Medicinal, and Cosmetic Value of Bioactive Compounds in Button Mushroom (Agaricus bisporus): A Review

Fungi are vital to numerous industrial and household processes, especially producing cheeses, beer, wine, and bread, and they are accountable for breaking down organic matter. The remarkable medicinal and nutritional values of the mushrooms have increased their consumption. Agaricus bisporus belongs to the Agaricaceae family, and it is a top-ranked cultivated mushroom that is well known for its edibility. A. bisporus is rich in nutrients such as carbohydrates, amino acids, fats, and minerals and has potential anticancer, antioxidant, anti-obesity, and anti-inflammation properties. The bioactive compounds extracted from this mushroom can be used for the treatment of several common human diseases including cancer, bacterial and fungal infections, diabetes, heart disorder, and skin problems. A. bisporus has opened new horizons for the world to explore mushrooms as far as their culinary and medicinal values are concerned. In recent years, tyrosinase and ergothioneine have been extracted from this mushroom, which has made this mushroom worth considering more for nutritional and medicinal purposes. To emphasize various aspects of A. bisporus, a comprehensive review highlighting the nutritional, medicinal, and cosmetic values and finding out the research gaps is presented. In this way, it would be possible to improve the quality and quantity of bioactive compounds in A. bisporus, ultimately contributing to the discovery of new drugs and the responsible mechanisms. In the present review, we summarize the latest advancements regarding the nutritional, pharmaceutical, and cosmetic properties of A. bisporus. Moreover, research gaps with future research directions are also discussed.

Structurally distinct external solvent-exposed domains drive replication of major human prions.

There is a limited understanding of structural attributes that encode the iatrogenic transmissibility and various phenotypes of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Here we report the detailed structural differences between major sCJD MM1, MM2, and VV2 prions determined with two complementary synchrotron hydroxyl radical footprinting techniques—mass spectrometry (MS) and conformation dependent immunoassay (CDI) with a panel of Europium-labeled antibodies. Both approaches clearly demonstrate that the phenotypically distant prions differ in a major way with regard to their structural organization, and synchrotron-generated hydroxyl radicals progressively inhibit their seeding potency in a strain and structure-specific manner. Moreover, the seeding rate of sCJD prions is primarily determined by strain-specific structural organization of solvent-exposed external domains of human prion particles that control the seeding activity. Structural characteristics of human prion strains suggest that subtle changes in the organization of surface domains play a critical role as a determinant of human prion infectivity, propagation rate, and targeting of specific brain structures.

Peripherally active dextromethorphan derivatives lower blood glucose levels by targeting pancreatic islets

Dextromethorphan (DXM) acts as cough suppressant via its central action. Cell-protective effects of this drug have been reported in peripheral tissues, making DXM potentially useful for treatment of several common human diseases, such as type 2 diabetes mellitus (T2DM). Pancreatic islets are among the peripheral tissues that positively respond to DXM, and anti-diabetic effects of DXM were observed in two placebo-controlled, randomized clinical trials in humans with T2DM. Since these effects were associated with central side effects, we here developed chemical derivatives of DXM that pass the blood-brain barrier to a significantly lower extent than the original drug. We show that basic nitrogen-containing residues block central adverse events of DXM without reducing its anti-diabetic effects, including the protection of human pancreatic islets from cell death. These results show how to chemically modify DXM, and possibly other morphinans, as to exclude central side effects, while targeting peripheral tissues, such as pancreatic islets.