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Oral administration of diphenyl diselenide protects against cadmium-induced liver damage in rats.

Cadmium is an environmental toxic metal implicated in human diseases. In the present study, the effect of diphenyl diselenide, (PhSe)(2), on sub-chronic exposure with cadmium chloride (CdCl(2)) was investigated in rats. Male adult Swiss albino rats received CdCl(2) (10 micromol/kg, orally) and (PhSe)(2) (5 micromol/kg, orally) for a period of 30 days. A number of parameters were examined as indicators of toxicity, including hepatic and renal damage, glucose and glycogen levels and markers of oxidative stress. Cadmium content, liver histology, delta-aminolevulinate dehydratase (delta-ALA-D) act

Efficacy of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and diphenyl diselenide on cadmium induced testicular damage in mice.

The deleterious effect of acute cadmium-intoxication in mice testes was evaluated. Animals received a single dose of CdCl2 (2.5 or 5 mg/kg, intraperitoneally) and a number of toxicological parameters in mice testes were examined, such as delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also determined. Thus, a possible protective effect of 2,3-dimercapt

Molecular basis of variegate porphyria: a de novo insertion mutation in the protoporphyrinogen oxidase gene.

The porphyrias are disorders that result from the inherited or acquired dysregulation of one of the eight enzymes in the heme biosynthetic pathway. Variegate porphyria (VP) is characterized by deficiencies in protoporphyrinogen oxidase (PPO) and has recently been genetically linked (Z = 6.62) to the PPO gene on chromosome 1q21. In this study, we have identified two sequence variants in the PPO gene in a family with VP. The first is a neutral polymorphism at the -47 position of intron 2; this polymorphism is present in the general population and is unlikely to underlie the VP phenotype. The sec

In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish.

Oxidative modification of LDL is an early pathological event in the development of atherosclerosis. Oxidation events such as malondialdehyde (MDA) formation may produce specific, immunogenic epitopes. Indeed, antibodies to MDA-derived epitopes are widely used in atherosclerosis research and have been demonstrated to enable cardiovascular imaging. In this study, we engineered a transgenic zebrafish with temperature-inducible expression of an EGFP-labeled single-chain human monoclonal antibody, IK17, which binds to MDA-LDL, and used optically transparent zebrafish larvae for imaging studies. Fee

δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system.

There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p=0.01). The Pb levels in blood (B-Pb) and urine (U-

Comprehensive analysis of acute flaccid paralysis with and without myelitis in Taiwanese children.

BACKGROUND: Acute flaccid paralysis (AFP) is a clinical syndrome marked by the sudden onset of muscle weakness or paralysis, requiring immediate medical intervention due to its potential for significant morbidity and mortality. Despite extensive studies on AFP, comparative analyses between cases with myelitis (M-AFP) and non-myelitis (NM-AFP) remain scarce. This study seeks to address this gap by analyzing demographic, clinical, and etiological distinctions between these groups. METHODS: A retrospective study was conducted on 39 pediatric AFP patients diagnosed between 2012 and 2021. Particip

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… Contractility History Taking and Blood Tests During an Episode/ acute paralysis NM-AFP16 (M/12y) hypoPP Potassium Ion Imbalance resulting in Impaired Muscle Contractility History Taking and Blood Tests During an Episode/ acute paralysis PM: Polymyositis; MSA: Myositis-Specific Autoantibodies; PGB: Porphobilinogen … Computed Tomography; ALL: Acute Lymphoblastic Leukemia; GBS: Guillain-Barre Syndrome; DTR: Deep Tendon Reflexes; hypoPP: Hypokalemic Periodic Paralysis Identified causes of acute flaccid paralysis without myelitis (NM-AFP) for 16 patients PM: Polymyositis; MSA: Myositis-Specific Autoantibodies; PGB: Porphobilinogen …

Активаторы Nrf2 для лечения редких заболеваний, связанных с перегрузкой железа: от скамейки до кровати.

Железная перегрузка и связанные с ней окислительные повреждения наблюдаются во многих редких болезнях в результате мутации генов, связанных с гомеостазом железа. Будучи основным регулятором реакции на клеточную антиоксидантную реакцию, Nrf2 может также снизить системный и клеточный уровень железа путем регулирования генов и путей, связанных с железом, что делает Nrf2 очень хорошими инициаторами для лечения нарушений, связанных с перегрузкой железа. К числу успешных примеров относится клиническое использование омавельоксолона для атаксии Фридрейха и диметилфумарата для повторного излучающего мн

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… Two water molecules are then extracted from ALA by ALA dehydratase to form porphobilinogen (PBG). Uroporphyrinogen synthase (UROS) catalyzed the conversion of hydroxymethylbilin to uroporphyrinogen III after PBG deaminase catalyzes the conversion of PBG to hydroxymethylbilin. … Two water molecules are then extracted from ALA by ALA dehydratase to form porphobilinogen (PBG). Uroporphyrinogen synthase (UROS) catalyzed the conversion of hydroxymethylbilin to uroporphyrinogen III after PBG deaminase catalyzes the conversion of PBG to hydroxymethylbilin. …

Keyword Index for Volume 90

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… platelet-derived growth factor 1068 PLC- γ 1 230 pleural cancer 1022 PLK1 414 PMLBCL 372 point mutation 1627 Polo-like kinase 815 poly-lysine 1252 polymers 2085, 2261 polymorphism 8, 419, 1809 poor prognosis 601 population mixing 1771 population pharmacokinetics 60 population-based 1382, 1572 porphobilinogen …

Current Advances in RNA Therapeutics for Human Diseases.

Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as the genetic code containing the necessary information for proper cell functioning. In the years following these discoveries, vast knowledge of the seemingly endless roles of RNA have become better understood. Additionally, many new types of RNAs were discovered that seemed to have no coding properties (non-coding RNAs), such as microRNAs (miRNAs). The discovery of these new RNAs created a new avenue for treating various human diseases. However, RNA is relatively unstable and is degraded fairl

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… This disorder is caused by a plethora of deficiencies in enzymes involved in heme production and leads to a toxic buildup of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) [ 127 ]. … Givosiran targets the mRNA of ALA synthase 1 in the liver and reduces the levels of disease-causing neurotoxic intermediates aminolevulinic acid and porphobilinogen [ 25 ]. Lumasiran was approved by the FDA for the treatment of primary hyperoxaluria type 1 (PH1) in 2020 [ 128 ]. …

Identification of markers of prostate cancer progression using candidate gene expression.

BackgroundMetastatic prostate cancer (PCa) has no curative treatment options. Some forms of PCa are indolent and slow growing, while others metastasise quickly and may prove fatal within a very short time. The basis of this variable prognosis is poorly understood, despite considerable research. The aim of this study was to identify markers associated with the progression of PCa.MethodsArtificial neuronal network analysis combined with data from literature and previous work produced a panel of putative PCa progression markers, which were used in a transcriptomic analysis of 29 radical prostatec

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… To provide information on inter- and intra-assay variation, reference genes included were included on each Taqman array: 18S , TBP (TATA box-binding protein), HPRT1 (hypoxanthine phosphoribosyltransferase 1), PBGD (porphobilinogen deaminase) and SDHA (succinate dehydrogenase complex, subunit A), which …

RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes to achieve posttranscriptional gene regulation. RNAi has proven to be an adaptable and powerful therapeutic strategy where advancements in chemistry and pharmaceutics continue to bring RNAi-based drugs into the clinic. With four siRNA medications already approved by the US Food and Drug Administration (FDA), several RNAi-based thera

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… Dysregulated ALAS1 expression is known to increase downstream production of neurotoxic metabolites, aminolevulinic acid, and porphobilinogen, causing AHP ( Anderson, 2019 ; Kothadia et al., 2022 ). … Clinical evidence shows that givosiran-treated patients saw a significant reduction in AHP attacks (74%) and sustained reduction in urinary aminolevulinic acid and porphobilinogen neurotoxic metabolite levels as well as decreased daily pain and an improved quality of life ( Balwani et al., 2020 ; Sardh …

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.

G protein-coupled receptors (GPCRs) are the major targets of existing drugs for a plethora of human diseases and dominate the pharmaceutical market. However, over 50% of the GPCRs remain undruggable. To pursue a breakthrough and overcome this situation, there is significant clinical research for developing RNA-based drugs specifically targeting GPCRs, but none has been approved so far. RNA therapeutics represent a unique and promising approach to selectively targeting previously undruggable targets, including undruggable GPCRs. However, the development of RNA therapeutics faces significant cha

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… lipid nanoparticle formulation was used to shield and stabilize the novel siRNA (ALN-18328) in patisiran from nuclease degradation. 98 In 2019, the FDA approved givosiran for the treatment of acute hepatic porphyria (AHP), which is caused by defective heme biosynthesis resulting in a toxic buildup of porphobilinogen … (PBG) and delta-aminolevulinic acid (ALA). 59 Givosiran targets the mRNA of ALA synthase 1 ( ALAS1 ) in the liver and reduces the serum levels of neurotoxic intermediates such as aminolevulinic acid and porphobilinogen. 99 Lumasiran was approved by the FDA in 2020 for the treatment of primary hyperoxaluria …

RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.

Background: RNA therapeutics represent a rapidly advancing field with significant potential for treating viral infections and cancer. This review examines the current landscape of RNA-based strategies, including siRNA, miRNA mimics, and antisense oligonucleotides. For viral infections, the focus is on hepatitis B (HBV) and C (HCV), HIV, and SARS-CoV-2. Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV). The successful development of mRNA vaccines for COVID-19 i

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… Improved quality of life, mobility, and nutritional status; Reduction in urinary aminolaevulinic acid (ALA) and porphobilinogen (PBG). …

Изучение точных методов лечения иммунизированных подстрекательских заболеваний: использование бесконечного потенциала доставки нуклеиновой кислоты.

Неизлечимые подстрекательские заболевания (ИМИД) создают неизмеримое бремя для отдельных лиц и общества. В то время как традиционное использование иммунодепрессантов и лекарственных средств для борьбы с заболеваниями обеспечивает частичную помощь и контроль, их неизбежные побочные эффекты и ограниченная эффективность ставят под сомнение возможность найти лекарство. Перспективные лекарства от нуклеиновой кислоты продемонстрировали способность оказывать точное воздействие на молекулярном уровне, при этом различные классы нуклеиновых кислот выполняют регулирующие функции с помощью различных механ

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… Inclisiran inhibits PCSK9 mRNA and thus lowers low‐density lipoprotein cholesterol levels. [ 29 ] Givosiran utilizes the ESC‐GalNAc delivery platform and targets the ALAS1 gene to reduce the accumulation of neurotoxic heme intermediates, including aminolevulinic acid (ALA) and porphobilinogen …

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies.

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic dr

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… Likewise, Ensafi et al. (2011) [ 72 ] constructed a porphobilinogen deaminase (PBGD) gene-detection probe. The PBGD gene is highly associated with CLL. …

Р

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Inpatient Medicine

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Abstracts of the ICARE 2024 78th SIAARTI National Congress

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63rd Annual Conference of the Indian Society of Gastroenterology, ISGCON 2022-January 5th - 8th, 2023 in Jaipur.

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Abstracts - IANCON 2024

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