Significance and Prospect of Brf1 Overexpression
Published on: 22nd August, 2023
Brf1 (TFIIB-related factor 1) is a transcription factor, which specifically modulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes), such as tRNAs and 5S rRNA. The products of tRNAs and 5S rRNA transcription will be changed with the alteration of Brf1 expression. Whereas deregulation of Brf1 and RNA Pol III genes are tightly associated with cell proliferation and transformation, and tumorigenesis. In recent years, emerging studies indicate that Brf1 expression is increased in patients with cancers. In this review, we summarize the progress of the abnormal expression of Brf1 in different human cancers to explore an underlying mechanism and its clinical implication, as well as to prompt its application prospect. With the depth of the Brf1 study and the progress of biotechnology, the status of Brf1 expression may be used as a universal indicator of the early detection and prognosis observation of human cancers.
Prospective Coronavirus Liver Effects: Available Knowledge
Published on: 18th August, 2023
The global pandemic COVID-19, caused by SARS-CoV-2, affected millions of people. COVID-19 is known for its respiratory symptoms, but new research reveals it may also affect other organ systems, including the liver. This abstract reviews COVID-19 and liver function. The virus enters host cells through liver-expressed angiotensin-converting enzyme 2 (ACE2) receptors. Thus, viral infection and replication may target the liver. Virus-induced inflammation and cytokine production may also harm the liver. ALT and AST elevations are the most prevalent liver abnormalities in COVID-19 patients. Liver function test abnormalities frequently indicate serious illness and poor clinical outcomes. COVID-19 may worsen pre-existing liver diseases such as NAFLD and chronic viral hepatitis. Drug-induced liver damage (DILI) from COVID-19 therapies including antivirals and corticosteroids complicates liver complications care. Recent investigations have also shown that COVID-19 may cause long-term liver damage. In conclusion, COVID-19 infection, immune-mediated damage, and treatment problems may severely compromise liver function. Optimizing patient treatment and discovering targeted medicines requires understanding COVID-19's liver role. To reduce the effects of COVID-19 on liver function, further study is required to understand the mechanisms and long-term effects.
A Novel Strategy to Improve Radiotherapy Effectiveness: First-in-Human MR-guided Focused Ultrasound-Stimulated Microbubbles (MRgFUS+MB) Radiation Enhancement Treatment
Published on: 24th August, 2023
Background and aim: Preclinical in vitro and in vivo experiments suggest that radiation-induced tumour cell death can be enhanced 10- to 40-fold when combined with focused-ultrasound (FUS)-stimulated microbubbles (MB). The acoustic exposure of MB in the tumour volume causes vasculature perturbation, activation of the acid sphingomyelinase (ASMase) ceramide pathway, and resultant endothelial cell apoptosis. When the tumour is subsequently treated with radiation, there is increased endothelial cell death and anoxic tumour killing. Here we describe a first-in-human experience treating patients with magnetic resonance (MR)-guided FUS-stimulated MB (MRgFUS+MB) radiation enhancement.Case presentation: A head and neck cancer patient with recurrent disease underwent radiotherapy for 5 separate sites of locoregional disease followed by systemic therapy. The first consisted of a course of 45 Gy in 5 fractions alone, the second of 30 Gy in 5 fractions with hyperthermia, and the three others of 20-30 Gy in 5 fractions along with MRgFUS+MB treatment. The treatment methodology used an MR-coupled FUS-device operating at 500 KHz and 540 kPa peak negative pressure with an insonification time of 750 ms spread over 5 minutes to stimulate intravenously administered MB within tumour target. All sites treated with stimulated MB had a complete radiological response, and subsequently, the patient’s other cutaneous metastatic disease disappeared. The patient has been under surveillance for over two years without active treatment or disease progression.Discussion: MRgFUS+MB was well-tolerated with no reported treatment-related adverse events, which can be attributed to the capability of FUS to selectively stimulate MB within the tumour volume while sparing the surrounding normal tissue. Sustained local control at all target sites aligns with earlier preclinical findings suggesting the radiation enhancement potential of FUS+MB.Conclusion: MRgFUS+MB represents a novel and promising therapy for enhancing radiation efficacy and improving therapeutic index with potential improvements in disease control.
Utilization of Molecular Simulation Applications for Stability Testing of Anthocyanin Compounds in Black Elderberry
Published on: 1st September, 2023
Recently, many studies on the molecular activity of compounds have been carried out using simulations through computer programs or in silico simulations. Anthocyanins are one of the compounds that are often used as food coloring agents and can function as antioxidants to prevent blockage of blood vessels, as an anti-cancer that can prevent the development of cancer cells and tumors and have anti-inflammatory effects. The purpose of the research is to determine the stability of anthocyanins using molecular simulations and determine the best mixing sequence of ingredients to produce the most stable anthocyanin mixture. Based on the results of the simulations carried out, it can be proven that the final 3 sets (the modeled compound belonging to namely AP and AZ followed by a number based on the simulation order) selected are AP17, AP18, and AZ17. The AP17 set had the lowest potential energy at the end of molecular dynamics simulations, but molecular visualization showed structural instability indicated by the formation of gaps in the molecular conformation. The AP18 set had the second lowest potential energy at the end of molecular dynamics simulations and molecular visualization showed molecular conformation that tended to be stable during molecular simulations with no change in structure. The AZ17 set had the highest potential energy of the final 3 sets selected and molecular visualization showed a gap in the conformation at the beginning of the simulation, but over time the gap became denser, indicating that the molecule became more stable over time. Based on the research results, the AP18 set was chosen because it has relatively low potential energy and it can be proven that the structure visualization of this set tends to be more stable over time during molecular dynamics simulations.
Microbial Conversion and Utilization of CO2
Published on: 4th September, 2023
Rising greenhouse gas emissions have contributed to unprecedented levels of climate change, while microbial conversion and utilization of CO2 is a practical way to reduce emissions and promote green manufacturing. This article mainly summarizes several natural CO2 pathways that have been discovered, including the Calvin cycle, the reduced tricarboxylic acid (rTCA) cycle, the Wood–Ljungdahl (WL) pathway, the 3-hydroxypropionate/4-hydroxybutyrate (HP/HB) cycle, the dicarboxylate/4-hydroxybutyrate (DC/HB) cycle, the 3-hydroxypropionate (3HP) cycle, the reductive glycine (rGly) pathway, and artificially designed carbon fixation pathways includes the CETCH cycle, the MOG pathway, the acetyl-CoA bicycle, and the POAP cycle. We also discussed applications of different carbon fixation enzymes, notably ribulose-1, 5-diphosphate carboxylase/oxygenase, pyruvate carboxylase, carbonic anhydrase, as well as formate dehydrogenase. This paper further addressed the development of photosynthetic autotrophs, chemergic autotrophs and model bacteria Escherichia coli or yeast produced main products for CO2 fixation through metabolic engineering, such as alcohols, organic acids, fatty acids and lipids, bioplastics, terpenoids, hydrocarbons, and biomass. Future studies on CO2 microbial conversion should focus on improving the efficiency of carbon fixation enzymes, metabolic modules of the carbon sequestration pathway, and intracellular energy utilization. Coupled microbial and electrochemical methods for CO2 fixation, in addition to biological fixation, show considerable promise.
Deep Venous Thrombosis as the Clinical Expression of POEMS Syndrome
Published on: 6th September, 2023
This case suggests that POEMS syndrome does present with a constellation of signs and symptoms that may lead a clinician to a multitude of other possible diagnoses. Diagnosis is often difficult and delayed. A good history and physical examination as well as a careful review of all workups are paramount in establishing this particular diagnosis. The major criteria of diagnostic for the syndrome are polyradiculoneuropathy, clonal plasma disorder, sclerotic bone lesions, the presence of Castleman disease, and elevated vascular endothelial growth factor. Minor features include organomegaly, extravascular volume overload, endocrinopathy, characteristic skin changes, papilledema, and thrombocytosis. The diagnosis is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. In this article, we discuss the differential diagnosis and outline the clinical evaluation indicated.
Case Report of a Child with Beta Thalassemia Major in a Tribal Region of India
Published on: 8th September, 2023
Introduction: Thalassemia is an inherited blood disorder of haemoglobin (Hb) synthesis, which affects different regions around the world. India has the largest number of children with beta-thalassemia major in the world, particularly in the tribal population. Heterozygous conditions are milder and even go unreported than the condition of homozygous where regular blood transfusion is required.Case report: This report focuses on a case of major beta-thalassemia in a child, whose parents are beta thalassemia minor to intermediate conditions, and who was treated by blood transfusion once a month. However, Thalassemia may be cured by allogeneic hematopoietic stem cell transplantation, although not everyone is a good candidate. Genetic counselling, prenatal diagnosis, and selective termination of affected fetuses are effective ways to control thalassemia.Discussion and conclusion: The paper reports a unique case of Thalassemia in rural India. The blood disorder while commonly presented in a juvenile whose parents were Thalassemia positive resulted in the termination of a fetus diagnosed with it. It archives the story of the parents who are now in the process of planning future offspring while mitigating disease risk. The case leads the way for effective management and containment of hereditary genetic disorders through carrier detection while planning alliances and offspring.
Multiparametric MRI for the Assessment of Treatment Effect and Tumor Recurrence in Soft-tissue Sarcoma of the Extremities
Published on: 20th September, 2023
Soft-tissue sarcomas are a rare and complex group of malignant tumors. Advanced MRI sequences such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging/dynamic contrast enhancement (PWI/DCE) can provide valuable tumor characterization and treatment response assessment. In the case of archetypical cellular tumors such as Pleomorphic Undifferentiated sarcoma (UPS), Good responders often display right-side displacement of the ADC intensity histogram, resulting in increased ADC-mean and decreased kurtosis and Skewness compared with Baseline and poor responders’ more left-sided curve. The PWI/DCE pattern most often associated with a good response is the presence of a “capsular-like” enhancement and a TIC type 2. Sarcoma hemorrhage patterns on SWI emerge during treatment, including “interstitial,” globular,” “luminal,” and incomplete and complete “peripheral ring-like” tumor wall hemosiderin impregnation. Treatment-induced bleeding is typically associated with low SWI-mean values and a left-sided intensity histogram with positive Skewness.During post-surgical surveillance, DCE MR imaging can reliably distinguish recurrent sarcoma from post-surgical scarring. TICs III, IV, and V raise the suspicion of local tumor recurrence, while TIC type II usually represents benign post-operative change such as granulation tissue. Advanced MRI is an essential tool for assessing sarcomas during and after therapy.
Determination of the Effect of Zinc Acetate as a Doped Substance on the Properties of Cadmium Sulfide Nanomaterials by using a Hydrothermal Interaction Technique
Published on: 14th September, 2023
In the current work, cadmium sulfide nanoparticles (CdS) NPs were synthesized via the hydrothermal interaction technique. Especially, the deviation in zinc Acetate Zn(CH3CO2)2 with 0.5% 1.5%, and 2.25% was examined for its part in nanoparticles size. The nanoparticle size seems to reduce from 149.7 nm to 116.3 nm by enhancing the zinc acetate Zn(CH3CO2)2. With increasing zinc acetate Zn(CH3CO2)2 in CdS (Cadmium Sulfide) small lattice phase changes appeared due to angle peaks of diffraction shifting toward higher angle. The standard crystallite size and lattice parameters were analyzed through X-ray diffraction (XRD) characterization. The average crystallite size and volume unit cell were found to increment with increasing Zinc acetate Zn(CH3CO2)2 concentrations. Absorption peaks in the UV visible spectra corresponding to zinc acetate Zn(CH3CO2)2 of CdS (Cadmium Sulfide) were analyzed at various wavelengths of 368 nm and 369 and 371nm. These findings show the tuning ability of structural, and optical characteristics of cadmium sulfide (CdS) NPs.
A Rare Case of an Acquired Isolated Factor VII Deficiency was Discovered in a 23-Year-Old Female Patient
Published on: 20th September, 2023
Introduction: Factor VII (FVII) deficiency, a rare bleeding disorder, can manifest as an autosomal recessive congenital or an acquired coagulopathy. Acquired FVII deficiency, although infrequently reported, presents unique challenges in understanding its mechanisms and identifying underlying causes. Case presentation: We present a case of acquired FVII deficiency discovered in a 23-year-old female patient with no apparent underlying disease. The patient exhibited spontaneous ecchymosis and gingival hemorrhage, along with low FVII activity and isolated prolongation of prothrombin time. Extensive laboratory investigations excluded liver dysfunction, familial deficiency, vitamin K deficiency, and inhibitory antibodies. Prompt treatment with Fresh Frozen Plasma (FFP) and bypassing agents resulted in a favorable response and resolution of hematomas. Conclusion: Acquired FVII deficiency was identified with bleeding symptoms in association with prolonged prothrombin time and a low level of FVII activity. In literature, this deficiency has been associated with various conditions such as sepsis, aplastic anemia, stem cell transplantation, and neoplasms, although approximately 14% of cases remain idiopathic. Clinical outcomes remain generally poor, with limited complete remissions reported.
Interconnection and Communication between Bone Marrow - The Central Immune System - And the Central Nervous System
Published on: 25th September, 2023
Bone marrow and the central nervous system are both protected by bone. The two systems are interconnected not only structurally but also functionally. In both systems specialized cells communicate through synapses. There exists a tridirectional communication within the neuroimmune network, including the hormonal system, the immune system, and the nervous system. Bone marrow is a priming site for T cell responses to blood-borne antigens including those from the central nervous system. In cases of auto (self) antigens, the responses lead to immune tolerance while in cases of neo (non-self) antigens, the responses lead to neoantigen-specific T cell activation, immune control, and finally to the generation of neoantigen-specific immunological memory. Bone marrow has an important function in the storage and maintenance of immunological memory. It is a multifunctional and very active cell-generating organ, constantly providing hematopoiesis and osteogenesis in finely-tuned homeostasis. Clinical perspectives include mesenchymal stem cell transplantation for tissue repair within the central nervous system.
Clinical Approach to Immunotherapy-induced Type 1 Diabetes Mellitus: A Case of Pembrolizumab Associated Insulin-dependent Diabetes in a Patient with NSCLC
Published on: 25th September, 2023
As the introduction of immune checkpoint inhibitors in the treatment of various cancers is now proven to be already acquired knowledge, so does a new challenge arise for clinicians; the understanding, diagnosis, and management of the rarest adverse effects of immunotherapy. We present a case of type-1 diabetes Mellitus (T1DM) in a patient with non-small cell lung carcinoma (NSCLC) treated with pembrolizumab. Following ten cycles of treatment, our patient was diagnosed with T1DM after being admitted for diabetic ketoacidosis and stayed hospitalized in the ICU. Later, they continued treatment with insulin, having shown disease response to pembrolizumab, and resumed immunotherapy while on insulin. Immunotherapy-induced T1DM can sometimes occur with PD1/PD-L1 blockage therapies. It has a rapid onset, is characterized by insulin deficiency due to the autoimmune destruction of beta-cells, and usually presents itself with diabetic ketoacidosis. Unlike most of the other adverse effects of immunotherapy, glucocorticoids don’t seem to be of therapeutic value, and insulin substitution is required. Regular glucose monitoring can be key to early diagnosis and prevention of hospitalization.
A Case of Catastrophic Atypical Hemolytic Uremic Syndrome Unresponsive to Eculizumab and the use of Ravulizumab Off-label
Published on: 5th October, 2023
“A 40-year-old woman with melanoma, under treatment with Dabrafenib and Trametinib, was evaluated in our hospital for rapidly progressive deterioration of renal function”. 8 months before the current admission, the patient had been diagnosed with melanoma, and underwent radical surgery and subsequent therapy with Dabrafenib and Trametinib.After 5 months of therapy, the patient was brought to this hospital for precordial pain, with a diagnosis of myopericarditis, therapy was started for heart failure with a good response. However, the patient developed a progressive impairment of renal function, associated with hemolytic anemia and thrombocytopenia. The peripheral smear showed the presence of schistocytes.The suspicion of atypical Hemolytic Uremic Syndrome (aHUS) was confirmed by the assay of C5B-9 induced by serum on endothelial cells, which showed a deposition of 331%, treatment with Eculizumab was initiated.After 3 administrations the patient did not improve, with further worsening of the hemolytic condition, and progression of renal damage.Due to the failure of Eculizumab, we considered the use of Ravulizumab. However, in Italy only can be administered to patients in Eculizumab stable treatment for at least three months. Nevertheless, faced with the catastrophic condition, it was decided to shift the therapy and use off-label Ravulizumab. After 10 days of the first administration, the laboratory tests showed a continuous rise in the values of haptoglobin, platelets, and hemoglobin, and a decrease in LDH. The renal function failed to return to normal values but after 20 days of therapy with Ravulizumab, there was complete resolution of the hemolytic condition.
Fetal Ductal Constriction due to Maternal Intake of Metamizole
Published on: 4th October, 2023
The prevalence of intra-uterine dysfunction of ductus arteriosus is unknown and the clinical consequences are poorly understood. We report a case of prenatal diagnosis of premature closure of the ductus arteriosus due to maternal intake of metamizole during pregnancy. Fetal echocardiography at 37 weeks of gestation revealed a right ventricular hypertrophy and suspected stenosis of the tricuspid valve. A cesarean section led to an excellent neonatal outcome. The aim of this report is to show echocardiographic abnormalities and outcomes of this rare phenomenom.
The Neuroprotective Role of TERT Influences the Expression of SOD1 in Motor Neurons and Mouse Brain: Implications for fALS
Published on: 14th October, 2023
Amyotrophic lateral sclerosis (ALS) disease is characterized by degeneration of motor neurons and elevation of brain oxidative stress. Previous studies demonstrated the neuroprotective effects of Telomerase reverse transcriptase (TERT) from oxidative stress. We showed that increasing TERT expression in the brain of the Tg hSOD1G93A mouse ALS model attenuated the disease pathology and increased the survival of motor neurons exposed to oxidative stress. How TERT increased the survival of motor neurons exposed to oxidative stress is not yet clear. Here we investigated the consequence of TERT depletion in motor neuron cells under normal and oxidative stress conditions and in mouse brains of TERT knockout mice, on the expression and activity of SOD1 and catalase enzymes. Depletion of mouse TERT caused mitochondrial dysfunction and impaired catalase and SOD1 activity. Compensation with hTERT restored the activity of SOD1. SOD1 expression increased in the brain of TERT KO and in ALS mice and decreased in the brain of WT mice treated with telomerase-increasing compounds. We suggest that the ability of TERT to protect neurons from oxidative stress affects the expression and activity of SOD1, in a TERT-dependent manner, and supports the notion of TERT as a therapeutic target for neurodegenerative diseases like ALS.
Production of L-Asparaginase by Yemeni Filamentous Fungi
Published on: 23rd October, 2023
Yemen with its diverse climatic regions represents a rich resource for bioactive compounds obtained from microorganisms. This study was designed to screen fungal isolates obtained from the Microbiology branch, Biological Sciences Department, Faculty of Science, Sana’a University for their ability to produce L-asparaginase enzyme. In preliminary screening for L-asparaginase, among 77 fungal isolates about 29 fungal isolates representing 37.66% were high producers of L-asparaginase. These fungal isolates belonged to the genera Aspergillus, Eupenicillium, Fusarium, Penicillium, and Stachyobotrys. These 29 fungal isolates were screened for their ability to produce L-asparaginase using the agar well diffusion method. 12 fungal isolates out of 29 showed the ability to produce extracellular L-asparaginase. These isolates belonged to 8 species which were: A. sulphurs, A. ustus, F. sacchari, P. chrysogenum, P. citrinum, P. corylophilum, P. melinii, and P. subturcoseum. Only 5 isolates were obtained for the determination of enzymatic activity, among them P. chrysogenum showed the highest activity (279.8696U ml-1) followed by A. ustus (170.9435U ml-1). This finding is the first report on the L-asparaginase production from filamentous fungi in Yemen.
Expression of Collagen VI, Anticollagenase, Laminin, MM9, Claudins 1 and 5, N and E Cadherins in Choroid Plexus Tumors
Published on: 25th November, 2023
Background: CPTs are rare intraventricular papillary neoplasms derived from the choroid plexus epithelium. Anti-collagenase and extracellular matrix which have not been expressed in brain tumors. Objective: The purpose of this study was to investigate the expression levels of collagen type VI, anti-collagenase, laminin, MM9, claudins 1 and 5, N and E cadherins, and collagen VII, tejido, and collagen degradation enzyme complexes in choroid plexus tumors.Materials and methods: We studied the expression of adhesion molecules, extracellular matrix, and anticollagenase with an immunohistochemistry approach and electron microscopy analysis in 42 choroid plexus tumors. Results: 28(67%) were choroid plexus papillomas, 8 (19%) were atypical choroid plexus papillomas and 6 (14%) were choroid plexus carcinomas. The Ki67-li and MVD increased from CPC to ACPP, being the highest in malignant tumors as well as a strong immunoexpression of anti-collagenase and were inverse correlation with claudin 5, E, and N cadherin and collagen IV immunoexpressions which added further significant information to the prognosis and varied according to the histologic classification. By ultrastructure, the loss of basal membrane and cilia, disorganization, and proliferation of ECM were observed in CPC. Cerebral homeostasis largely results from the ability of both the Blood–Brain Barrier (BBB) at the brain microvascular endothelium and the Blood–Cerebrospinal Fluid Barrier (BCSFB) at the epithelium of the Choroid Plexuses (CPs), to control the composition of the CSF and cerebral extracellular fluid. Under expression of the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular abnormalities responsible for the increased permeability of tumor endothelial tight junctions. Conclusion: The loss of basement membrane and ECM overexpression could be considered as a poor prognosis predictor in CPT. Anti-collagenase and MMP9 overexpression could be related to basal membrane and BBB plasticity in CPTs.
An Executive Information System: Inherent Information and Functional Information
Published on: 31st October, 2023
This review article deals with quantum biology, the new tool that helps traditional biology unravel some mysteries concerning life and living organisms on Earth. We use Einstein’s famous equation to explain how an unknown energy realm creates the material universe. We demonstrate how material existence precedes living existence and elucidate how non-living atoms transition to living molecules, Francis Crick’s faded dream that comes to reality. Finally, we expose the two types of Information available inside a cell to sustain life in living organisms and elaborate on a new formulation of the biogenesis theory.
Masquelet Technique for Reconstruction of a Fourth Metatarsal Defect Following a Low-velocity Gunshot Wound: A Case Report
Published on: 2nd November, 2023
The Masquelet technique has become increasingly popular in reconstruction scenarios such as osteomyelitis, cancer, and nonunions. The procedure is a two-staged approach: first, a polymethylmethacrylate (PMMA) cement spacer is inserted to fill a bone void. The spacer induces a membrane to form around it, and 6-9 weeks later, the second stage involves carefully extracting the spacer and filling the membrane with bone graft. Most of the current literature has published either femoral or tibial involvement for Masquelet studies, with limited published data on foot reconstruction. Here, the authors used the procedure for the fourth metatarsal. Despite complications, this case proves a more excellent utility and warrants further investigation into Masquelet techniques in the foot.
Gene Expression and Functional Analysis in Patients with Acute and Chronic Renal Allograft Rejection
Published on: 3rd November, 2023
Kidney transplantation is the therapy of choice for patients with end-stage kidney disease (ESKD). Nevertheless, the main limitation for long-term graft survival is immune-mediated rejection. Some authors have proposed that differences in immune effector mechanisms are influenced by underlying molecular mechanisms; thereby, the identification of differentially expressed genes in acute or chronic rejection in non-invasive samples such as urine may be essential for the identification of potential biomarkers and biological processes associated with allograft outcomes. Our aim was to explore differences in gene expression and functional categories associated with acute and chronic kidney rejection in blood, biopsy, and urine of kidney transplant patients using RNA-Seq. RNA was isolated and sequenced implementing standard protocols. Analyses were addressed to identify differentially expressed genes (DEGs) and Functional Categories of Gene Ontology comparing between samples. Then we focused on immune genes and pathways to identify their association with the allograft. We identified a significant transcriptional similarity between biopsy and urine, in comparison with blood in acute and chronic rejection. Functional analyses suggested an enrichment of immune processes such as antigen processing and presentation, and regulation of B cell receptor signaling pathway in blood of acute and chronic rejection, respectively. Additionally, we observed an increase in expression of chemokines in biopsy and urine of both outcomes along with an increase in chemokine receptors in blood. Our findings suggest that urine is suitable for identifying potential biomarkers and biological processes related to renal allograft rejection, as it shares a significant number of regulated genes with biopsy.
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