Common Human Diseases Research Articles

5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy.

5-Aminolevulinic acid (ALA) is a naturally occurring amino acid synthesized in all nucleated mammalian cells. As a porphyrin precursor, ALA is metabolized in the heme biosynthetic pathway to produce protoporphyrin IX (PpIX), a fluorophore and photosensitizing agent. ALA administered exogenously bypasses the rate-limit step in the pathway, resulting in PpIX accumulation in tumor tissues. Such tumor-selective PpIX disposition following ALA administration has been exploited for tumor fluorescence diagnosis and photodynamic therapy (PDT) with much success. Five ALA-based drugs have now received worldwide approval and are being used for managing very common human (pre)cancerous diseases such as actinic keratosis and basal cell carcinoma or guiding the surgery of bladder cancer and high-grade gliomas, making it the most successful drug discovery and development endeavor in PDT and photodiagnosis. The potential of ALA-induced PpIX as a fluorescent theranostic agent is, however, yet to be fully fulfilled. In this review, we would like to describe the heme biosynthesis pathway in which PpIX is produced from ALA and its derivatives, summarize current clinical applications of ALA-based drugs, and discuss strategies for enhancing ALA-induced PpIX fluorescence and PDT response. Our goal is two-fold: to highlight the successes of ALA-based drugs in clinical practice, and to stimulate the multidisciplinary collaboration that has brought the current success and will continue to usher in more landmark advances.

The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol

BackgroundCreutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.MethodsThe study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an “in-depth” visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a “brief” visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one “in-depth” visit, similar to the baseline visit of healthy relatives.DiscussionThis continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions.Trial registrationThe study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.

Substance P aggravates ligature-induced periodontitis in mice.

Periodontitis is one of the most common oral diseases in humans, affecting over 40% of adult Americans. Pain-sensing nerves, or nociceptors, sense local environmental changes and often contain neuropeptides. Recent studies have suggested that nociceptors magnify host response and regulate bone loss in the periodontium. A subset of nociceptors projected to periodontium contains neuropeptides, such as calcitonin gene-related peptide (CGRP) or substance P (SP). However, the specific roles of neuropeptides from nociceptive neural terminals in periodontitis remain to be determined. In this study, we investigated the roles of neuropeptides on host responses and bone loss in ligature-induced periodontitis. Deletion of tachykinin precursor 1 (Tac1), a gene that encodes SP, or treatment of gingiva with SP antagonist significantly reduced bone loss in ligature-induced periodontitis, whereas deletion of calcitonin related polypeptide alpha (Calca), a gene that encodes CGRP, showed a marginal role on bone loss. Ligature-induced recruitment of leukocytes, including neutrophils, and increase in cytokines leading to bone loss in periodontium was significantly less in Tac1 knockout mice. Furthermore, intra-gingival injection of SP, but not neurokinin A, induced a vigorous inflammatory response and osteoclast activation in alveolar bone and facilitated bone loss in ligature-induced periodontitis. Altogether, our data suggest that SP plays significant roles in regulating host responses and bone resorption in ligature-induced periodontitis.

Consumer Perception, Nutritional, and Technological Properties of Bread Made with Chickpea Flour

Celiac disease (CD) is one of the most common intestinal diseases in humans today. The only "cure" for this disease is a strictly gluten-free diet. Bread is a highly accepted food product. But, bread is a product that owns its technological properties to the presence of gluten. Bread without gluten has different texture, palatability, and sensorial properties. Therefore, new products are needed to solve this problem. Chickpeas are an inexpensive source of protein for making gluten-free baked goods. In this study, we explored a gluten-free bread formula made with chickpea flour and examined the consumer profile of chickpea bread and its nutritional and technical properties. Results showed that chickpeas could be an alternative raw material for meeting the consumer needs of people who need (or prefer) gluten-free products/diets.

Prion Diseases

Prions refer to abnormal misfolded proteins which propagate rare, rapidly progressive, and inevitably fatal neurodegenerative infectious diseases affecting both humans and non-human mammals. The most common human prion disease is Creudtzfeldt-Jakob disease (CJD), aetiologically categorized as either (1) sporadic (sCJD), (2) acquired via infection (aCJD), (3) hereditary (hCJD), or (4) variant (vCJD). vCJD, in particular, is commonly known due to its contraction via consumption of beef infected with Bovine Spongiform Encephalopathy, also known as Mad Cow Disease: a similarly fatal prion disease affecting cows. Regardless of the causative mechanism, all CJDs are characterized by the rapid decline in cognitive function, myoclonus (involuntary twitching and/or jerking of muscles), akinetic mutism, and ultimately, death in all cases. As suggested by the aforementioned symptoms, CJD is considered a rapidly progressive dementia (RPD), alongside Alzheimer’s, Huntington’s, and Parkinson’s disease.

Machine learning aided multiscale modelling of the HIV-1 infection in the presence of NRTI therapy.

Human Immunodeficiency Virus (HIV) is one of the most common chronic infectious diseases in humans. Extending the expected lifetime of patients depends on the use of optimal antiretroviral therapies. Emergence of the drug-resistant strains can reduce the effectiveness of treatments and lead to Acquired Immunodeficiency Syndrome (AIDS), even with antiretroviral therapy. Investigating the genotype-phenotype relationship is a crucial process for optimizing the therapy protocols of the patients. Here, a mathematical modelling framework is proposed to address the impact of existing mutations, timing of initiation, and adherence levels of nucleotide reverse transcriptase inhibitors (NRTIs) on the evolutionary dynamics of the virus strains. For the first time, the existing Stanford HIV drug resistance data have been combined with a multi-strain within-host ordinary differential equation (ODE) model to track the dynamics of the most common NRTI-resistant strains. Overall, the D4T-3TC, D4T-AZT and TDF-D4T drug combinations have been shown to provide higher success rates in preventing treatment failure and further drug resistance. The results are in line with the genotype-phenotype data and pharmacokinetic parameters of the NRTI inhibitors. Moreover, we show that the undetectable mutant strains at the diagnosis have a significant effect on the success/failure rates of the NRTI treatments. Predictions on undetectable strains through our multi-strain within-host model yielded the possible role of viral evolution on the treatment outcomes. It has been recognized that the improvement of multi-scale models can contribute to the understanding of the evolutionary dynamics, and treatment options, and potentially increase the reliability of genotype-phenotype models.

Expression Pattern and Value of Brain-Derived Neurotrophic Factor in Periodontitis

BackgroundPeriodontitis is a common human disease with an increasing incidence. Brain-derived neurotrophic factor (BDNF) is known to play a crucial role in the regeneration of periodontal tissue; however, the expression, methylation level, molecular function, and clinical value of BDNF in periodontitis require further investigation. This study aimed to investigate the expression and potential functions of BDNF in periodontitis. MethodsRNA expression and methylation data were obtained from the Gene Expression Omnibus (GEO) database, and the expression and methylation levels of BDNF were compared between periodontitis and normal tissues. In addition, bioinformatics analysis was performed to investigate the downstream molecular functions of BDNF. Finally, Reverse transcription Quantitative real-time polymerase chain reaction was performed to determine the level of BDNF expression in periodontitis and normal tissues. ResultsGEO database analysis revealed that BDNF was hypermethylated in periodontitis tissues and that its expression was downregulated. Reverse transcription Quantitative real-time polymerase chain reaction confirmed that BDNF expression was downregulated in periodontitis tissues. Several genes that interact with BDNF were determined using a protein–protein interaction network. Functional analysis of BDNF revealed that it was enriched in the Gene Ontology terms cytoplasmic dynein complex, glutathione transferase activity, and glycoside metabolic process. Kyoto Encyclopedia of Genes and Genomes analysis suggested that BDNF was associated with the mechanistic target of rapamycin signaling pathway, fatty acid metabolism, the Janus kinase-signal transducer and activator of transcription signaling pathway, glutathione metabolism, and others. Furthermore, the level of BDNF expression was correlated with the immune infiltration degree of B cells and CD4+ T cells. ConclusionsThis study shown that BDNF was hypermethylated and downregulated in periodontitis tissues, which could be a biomarker and treatment target of periodontitis.

Mussel-Inspired Caries Management Strategy: Constructing a Tribioactive Tooth Surface with Remineralization, Antibiofilm, and Anti-inflammation Activity.

Dental caries is a common chronic oral disease in humans resulting from tooth demineralization caused by acid production of bacterial plaque, which leads to the destruction of enamel and dentin and oral inflammation. However, it is still a challenge that the function of natural active ingredients in currently available oral care products is not comprehensive, especially the lack of remineralization. Here, inspired by the strong biological adhesion ability of mussels and ancient oral disease plant therapy, a multifunctional strategy is proposed to construct a bioactive tooth surface to treat dental caries. It has been demonstrated that the Turkish gall extract (TGE) can inhibit adhesion of cariogenic bacteria Streptococcus mutans and Actinomyces viscosus and destroy biofilms on the tooth surface. Meanwhile, TGE can reduce the expression of inflammatory factors. Notably, the TGE coating can induce the growth of hydroxyapatite (HAP) crystals in vivo and in vitro, recovering the enamel mechanical properties under normal oral conditions. MD simulations interpreted the adsorption mechanism by which the hydroxyl groups in TGE bind to phosphate group (PO43-) on the tooth surface, attracting calcium ions (Ca2+) as nucleation sites for remineralization. This work underlines the importance of TGE coating in remineralization, antibiofilm, and anti-inflammation activity as a promising strategy for dental caries.

Native functions of short tandem repeats.

Over a third of the human genome is comprised of repetitive sequences, including more than a million short tandem repeats (STRs). While studies of the pathologic consequences of repeat expansions that cause syndromic human diseases are extensive, the potential native functions of STRs are often ignored. Here, we summarize a growing body of research into the normal biological functions for repetitive elements across the genome, with a particular focus on the roles of STRs in regulating gene expression. We propose reconceptualizing the pathogenic consequences of repeat expansions as aberrancies in normal gene regulation. From this altered viewpoint, we predict that future work will reveal broader roles for STRs in neuronal function and as risk alleles for more common human neurological diseases.

Enhanced effect of a novel bioactive glass-ceramic for dental application.

Dental caries is the most common chronic disease in humans, caused by the acid produced by the microflora in the mouth that dissolves the enamel minerals. Bioactive glass (BAG) has been used in various clinical applications due to its unique bioactive properties, such as bone graft substitutes and dental restorative composites. In this study, we introduce a novel bioactive glass-ceramic (NBGC) prepared through a sol-gel process under a water-free condition. The anti-demineralization and remineralization effects of NBGC were evaluated by comparing the measurements of bovine enamel surface morphology, surface roughness, surface micro-hardness, enamel elements, and mineral content before and after related treatments with a commercial BAG. The antibacterial effect was characterized by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Results showed that NBGC had greater acid resistance and remineralization potential compared to commercial BAG. The fast formation of a hydroxy carbonate apatite (HCA) layer suggests efficient bioactivity. In addition to its antibacterial properties, NBGC shows promise as an ingredient in oral care products that can prevent demineralization and restore enamel.

Bioactive Molecules Derived from Plants in Managing Dengue Vector Aedes aegypti (Linn.).

Mosquitoes are the potential vectors of several viral diseases such as filariasis, malaria, dengue, yellow fever, Zika fever and encephalitis in humans as well as other species. Dengue, the most common mosquito-borne disease in humans caused by the dengue virus is transmitted by the vector Ae. aegypti. Fever, chills, nausea and neurological disorders are the frequent symptoms of Zika and dengue. Thanks to various anthropogenic activities such as deforestation, industrialized farming and poor drainage facilities there has been a significant rise in mosquitoes and vector-borne diseases. Control measures such as the destruction of mosquito breeding places, a reduction in global warming, as well as the use of natural and chemical repellents, mainly DEET, picaridin, temephos and IR-3535 have proven to be effective in many instances. Although potent, these chemicals cause swelling, rashes, and eye irritation in adults and children, and are also toxic to the skin and nervous system. Due to their shorter protection period and harmful nature towards non-target organisms, the use of chemical repellents is greatly reduced, and more research and development is taking place in the field of plant-derived repellents, which are found to be selective, biodegradable and harmless to non-target species. Many tribal and rural communities across the world have been using plant-based extracts since ancient times for various traditional and medical purposes, and to ward off mosquitoes and various other insects. In this regard, new species of plants are being identified through ethnobotanical surveys and tested for their repellency against Ae. aegypti. This review aims to provide insight into many such plant extracts, essential oils and their metabolites, which have been tested for their mosquitocidal activity against different life cycle forms of Ae. Aegypti, as well as for their efficacy in controlling mosquitoes.

Association of S19W polymorphism in APOA5 gene and serum lipid levels in patients with type 2 diabetic nephropathy.

Type 2 diabetic Mellitus (T2DM) is the most common systemic and endocrine disease in humans, anddiabetic nephropathy is one of the most serious complications of this disorder. The polymorphisms in the apolipoprotein A5 (ApoA5) gene are strongly related to hypertriglyceridemia and are considered a predisposing factor for diabetic nephropathy. The current study proposed to examine the association of APOA5-S19W polymorphism with serum lipids levels in patients with type 2 diabetic nephropathy in Mazandaran province. This case-control study was designed to determine the association of APOA5-S19W polymorphism with plasma lipid profile in 161 T2DM patients with nephropathy (DN+), without nephropathy (DN-), and in 58 healthy individuals. Lipid profile values were measured using ParsAzmoun commercial kits. S19W variant, one of the polymorphisms of the APOA5 gene, was determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and Taq1 restriction enzyme. In comparison between the three groups, DN+ had a higher mean TG than DN- and the control group (p<0.001). The incidence of the G allele in DN+ was not significant compared to groups of DN-. Comparing the relationship between the mean of biochemical variables with CC and CG genotypes showed that the mean level of TG in people with CC genotype was increased compared to people with CG genotype in diabetic patients. However, this increase was not significant (p=0.19). There was no association between SNP APOA5 S19W and serum lipids in diabetic patients with and without nephropathy.

Regenerative Potential of Bone Morphogenetic Protein 7-Engineered Mesenchymal Stem Cells in Ligature-Induced Periodontitis.

Periodontitis is an oral disease caused by bacterial infection that has stages according to the severity of tissue destruction. The advanced stage of periodontitis presents irreversible destruction of soft and hard tissues, which finally results in loss of teeth. When conventional treatment modalities show limited results, tissue regeneration therapy is required in patients with advanced periodontitis. In the present study, we aimed to evaluate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) delivering bone morphogenetic protein 7 (BMP7) on tissue regeneration in a periodontitis model. BMP7 is a member of the BMP family that shows bone-forming ability; however, BMPs rapid clearing and degradation and unproven efficacy make it difficult to apply it in clinical dentistry. To overcome this, we established BMP7-expressing engineered BM-MSCs (BMP7-eBMSCs) that showed superior osteogenic differentiation potential when subcutaneously transplanted with a biphasic calcium phosphate scaffold into immunocompromised mice. Furthermore, the efficacy of BMP7-eBMSC transplantation for periodontal tissue regeneration was evaluated in a rat ligature-induced periodontitis model. Upon measuring two-dimensional and three-dimensional amounts of regenerated alveolar bone using microcomputed tomography, the amounts were found to be significantly higher in the BMP7-eBMSC transplantation group than in the eBMSC transplantation group. Most importantly, fibrous periodontal ligament (PDL) tissue regeneration was also achieved upon BMP7-eBMSC transplantation, which was evaluated by calculating the modified relative connective tissue attachment. The amount of connective tissue attachment in the BMP7-eBMSC transplantation group was significantly higher than that in the ligature-induced periodontitis group, although the increase was comparable between the BMP7-eBMSC and human PDL stem cell transplantation groups. Taken together, our results suggested that sustainable release of BMP7 induces periodontal tissue regeneration and that transplantation of BMP7-eBMSCs is a feasible treatment option for periodontal regeneration. Impact Statement Periodontitis is the second most common human dental disease affecting chronic systemic diseases. Despite the tremendous efforts trying to cure the damaged periodontal tissues using tissue engineering technologies, a definitive regenerative method has not been in consensus. Researchers are seeking more feasible and abundant source of mesenchymal stem cells (MSCs), and furthermore, how to use reliable growth factors under more efficient control are the issues to be solved. In this study, we aimed to evaluate the effect of bone morphogenetic protein 7 (BMP7) gene delivering bone marrow-derived MSCs on periodontal tissue regeneration to evaluate the efficacy of BMP7 and engineered BMSCs for periodontal tissue regeneration.

Recombinant Probiotic Preparations: Current State, Development and Application Prospects

The article is devoted to the latest achievements in the field of research, development, and implementation of various types of medicinal products based on recombinant probiotics. The benefits of probiotics, their modern use in medicine along with the most frequently used genera and species of probiotic microorganisms were highlighted. The medicinal and therapeutic activities of the studied probiotics were indicated. The review suggests various methods of creating recombinant probiotic microorganisms, including standard genetic engineering methods, as well as systems biology approaches and new methods of using the CRISPR-Cas system. The range of potential therapeutic applications of drugs based on recombinant probiotics was proposed. Special attention was paid to modern research on the creation of new, more effective recombinant probiotics that can be used for various therapeutic purposes. Considering the vast diversity of therapeutic applications of recombinant probiotics and ambiguous functions, their use for the potential treatment of various common human diseases (non-infectious and infectious diseases of the gastrointestinal tract, metabolic disorders, and allergic conditions) was investigated. The prospects for creating different types of vaccines based on recombinant probiotics together with the prospects for their implementation into medicine were considered. The possibilities of using recombinant probiotics in veterinary medicine, particularly for the prevention of domestic animal diseases, were reviewed. The prospects for the implementation of recombinant probiotics as vaccines and diagnostic tools for testing certain diseases as well as modeling the work of the human digestive system were highlighted. The risks of creation, application, including the issues related to the regulatory sphere regarding the use of new recombinant microorganisms, which can potentially enter the environment and cause unforeseen circumstances, were outlined.

Detection of Pulmonary Tuberculosis by Gene Xpert Method among HIV Patient in ART Center, Gadarif State, Sudan

Background: Tuberculosis (TB) is one of the most common and deadly infectious diseases in humans. Due to widespread poverty, inequity, and conflict, suboptimal health services in many countries, and the impact of the HIV/AIDS pandemic, TB/HIV co-infected patients frequently test negative for TB with direct microscopy, posing diagnostic challenges. Traditional HIV-associated TB diagnosis is complex, expensive, time-consuming, and technically demanding because it relies on conventional culture and drug susceptibility testing. The lengthy wait for results has disastrous consequences for patients who go undiagnosed or are diagnosed too late.&#x0D; Objective: To detect the accuracy of gene X pert® MTB/RIF as a novel automated molecular tool to diagnose Mycobacterium tuberculosis in HIV patients.&#x0D; Methods: A cross sectional study was conducted on 70 HIV patients suspected to have Mycobacterium tuberculosis and who were referred to the ART and Tuberculosis Centers at Gadarif state, from June 2022 to December 2022. Sputum samples were tested by two methods involved the Gene X pert (Cepheid, California, United States of America) and direct smear microscopy (SM) stained with ZN stain for detection of acid fast bacilli. Out of 70 sputum samples analyzed for acid fast bacilli, 50(71%) cases were positive using GeneXpert whereas the DM was positive only for 28 (4o %) of the cases. GeneXpert detected another 22 AFB positive cases. Therefore GeneXpert is more accurate. Sensitivity of the GeneXpert was calculated as 93% and the specificity was 43%. The majority of the patients who contributed to (SM) were found to be co-infected with HIV.&#x0D; Conclusion: GeneXpert demonstrated two-time case detection rate compared to the sputum smear microscopy so the direct smear showed poor performance tool for evaluation of TB-HIV co-infection. Also The Gene X pert’s sensitivity was found to be high while the specificity was low. Although this was the case, the GeneXpert as compared to DM could greatly reduce false negatives and the wait on treatment initiation can be significantly shortened, minimising premature death and continued transmission.

Potential Beneficial Effects of Hydroxyapatite Nanoparticles on Caries Lesions In Vitro-A Review of the Literature.

Dental caries is one of the most common human diseases which can occur in both primary and permanent dentitions throughout the life of an individual. Hydroxyapatite is the major inorganic component of human teeth, consequently, nanosized hydroxyapatite (nHAP) has recently attracted researchers' attention due to its unique properties and potential for caries management. This article provides a contemporary review of the potential beneficial effects of nHAP on caries lesions demonstrated in in vitro studies. Data showed that nHAP has potential to promote mineralization in initial caries, by being incorporated into the porous tooth structure, which resulted from the caries process, and subsequently increased mineral content and hardness. Notably, it is the particle size of nHAP which plays an important role in the mineralization process. Antimicrobial effects of nHAP can also be achieved by metal substitution in nHAP. Dual action property (mineralizing and antimicrobial) and enhanced chemical stability and bioactivity of nHAP can potentially be obtained using metal-substituted fluorhydroxyapatite nanoparticles. This provides a promising synergistic strategy which should be explored in further clinical research to enable the development of dental therapeutics for use in the treatment and management of caries.

Evaluation of Shear Bond Strengths of Three Adhesive Materials Used to Retain Fiber Post in the Severely Damaged Primary Anterior Teeth

Background and Objective: Tooth decay and periodontal problems are among the most common human diseases which are considered unsolved health problems in most countries of the world. This study aimed to investigate and compare the shear bond strength of the fiber post with three different types of cement, including Glass ionomer, as well as Universal and Flowable composites. Materials and Methods: This in-vitro study was conducted on 30 extracted anterior deciduous teeth with at least two-thirds of healthy roots. The teeth were randomly divided into three groups of 10. The teeth were mounted from the root part inside the self-curing acryl. Group 1 includes G-Premio Bond and Universal Composite, group 2 includes G-Premio Bond and flowable composite, and group 3 includes Glass ionomer without bond. Immediately, the fiber post was placed in the cemented material in the canal and was light-cured according to the manufacturer's instructions. Shear bond strength was performed by an electromechanical universal testing machine at a speed of 1 mm/min. Results: The shear bond strength mean values in the Universal composite, Glass ionomer, and Flowable composite groups were 15.29±4.82, 9.74±2.82, and 13.71±4.91 MPa, respectively, and the difference among them was significant (P=0.022). The shear bond strength mean value of the Universal composite was significantly higher than that of the Glass ionomer (P=0.020); however, this difference was not significant for comparing other groups (P&lt;0.05). Conclusion: The highest and lowest amount of shear bond strength values for cementing fiber post in the repair of anterior deciduous teeth were related to the Universal composite and Glass ionomer cement groups, respectively, which showed a significant difference but did not differ significantly from the Flowable composite group

Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis.

Genetics of Familial Hypercholesterolemia (FH) is ascribable to pathogenic variants in genes encoding proteins leading to an impaired LDL uptake by the LDL receptor (LDLR). Two forms of the disease are possible, heterozygous (HeFH) and homozygous (HoFH), caused by one or two pathogenic variants, respectively, in the three main genes that are responsible for the autosomal dominant disease: LDLR, APOB and PCSK9 genes. The HeFH is the most common genetic disease in humans, being the prevalence about 1:300. Variants in the LDLRAP1 gene causes FH with a recessive inheritance and a specific APOE variant was described as causative of FH, contributing to increase FH genetic heterogeneity. In addition, variants in genes causing other dyslipidemias showing phenotypes overlapping with FH may mimic FH in patients without causative variants (FH-phenocopies; ABCG5, ABCG8, CYP27A1 and LIPA genes) or act as phenotype modifiers in patients with a pathogenic variant in a causative gene. The presence of several common variants was also considered a genetic basis of FH and several polygenic risk scores (PRS) have been described. The presence of a variant in modifier genes or high PRS in HeFH further exacerbates the phenotype, partially justifying its variability among patients. This review aims to report the updates on the genetic and molecular bases of FH with their implication for molecular diagnosis.

Dermatitis Atopic and Psoriasis Skin Disease Classification by using Convolutional Neural Network

Skin is the one of the body parts that play a large role in human physical body. There are so many functions of the skin such as offering protection against fungal infection, bacteria, allergy, viruses and controls the temperature of the body. But, the reported shown that the skin disease is the most common disease in humans among all age groups and a significant root of infection. The diagnosis of skin diseases involves several tests. Due to this, the diagnosis process is seen to be intensely laborious, time-consuming and requires an extensive understanding aspecially for the skin disease that have similar symptoms. Two skin diseases that have similar symptoms and most misdiagnosed are atopic dermatitis and psoriasis. Convolutional Neural Network for image processing and classifying have been developed for more accurate classification of skin diseases with different architectures. However, the accuracy in determining skin lesions using CNNs is on the average level. The factors that affect the accuracy result of a CNN is the depth where gradients vanished as the network goes deeper. Another factor is the variance in the training set which means the need of the large size of training set. Hence, in this study we tried 10 CNN architecture to get the best result for classifying dermatitis atopic and psoriasis. These are VGG 16, VGG 19, ResNet 50, ResNet 101, MobileNet, MobileNet V2, DenseNet 121, DenseNet 201, Inception and Xception. Experimental result shown that the inception V3 architecture give the best result with accuracy for data testing 84%, accuracy for unseen data 82% and confusion matrix with True positive obtained is 248, True Negative is 61, False positive is 54 and False Negative 298.

Synthesis, in silico, in vitro and in vivo studies of novel natural-based arylidenes curcumin as potential glycohydrolase digestive enzymes inhibitors

Diabetes is one of the most common metabolic diseases in humans and the use of herbal medicines is of great clinical importance to inhibit carbohydrate-hydrolyzing enzymes and reduce blood glucose levels in diabetic patients. Inhibition of glycosidase activity is an effective way to treat and prevent diabetes. Therefore, in this study, curcumin-based benzaldehyde derivatives were synthesized and used as influential agents in the treatment of diabetes with inhibitory properties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Glu) and α-amylase (α-Amy) as significant therapeutic targets for reducing postprandial hyperglycemia. Overall, the findings showed that due to the specific inhibitory activity against α-Glu in comparison with α-Amy, as well as more stability and antioxidant activity than curcumin, C5 and C8 derivatives are potentially important anti-diabetic drugs, not only to decrease glycemic index but also to limit the activity of the main production pathways of reactive oxygen species (ROS) in diabetic patients. Communicated by Ramaswamy H. Sarma