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Case Reports in Dermatology 2022Lichen planus is a chronic, inflammatory, immune-mediated dermatosis affecting the patient's skin, scalp, mucous membranes, and nails. Drug-induced lichen planus is...
Lichen planus is a chronic, inflammatory, immune-mediated dermatosis affecting the patient's skin, scalp, mucous membranes, and nails. Drug-induced lichen planus is described after the administration of antimalarials, ß-blockers, methyldopa, NSAIDs, penicillamines, and sodium aurothiomalate. The use of biologicals such as adalimumab, etanercept, and infliximab has also been linked with the appearance of lichenoid eruptions in the recent past. In this case, we report on a patient developing oral and cutaneous lichen planus after the administration of dupilumab. The lichenoid lesions occurred after 11 months of the drug's administration and involved the buccal walls, trunk, and extremities. Dupilumab had been administered in an effort to counter severe atopic dermatitis exacerbations. Dupilumab is associated with a downregulation of T-helper 2 cell activation by blocking the Interleukin-4/Interleukin-13 pathway, so leading to a TH1/TH2 imbalance. This imbalance may cause a shift toward a TH1-mediated immune response and be an explanation for the drug-induced lichen planus. Dupilumab was discontinued, and the patient was treated with oral corticosteroids and UVB phototherapy, leading to a significant improvement in the lichen planus lesions.
PubMed: 36655064
DOI: 10.1159/000527918 -
Microbiological Research Mar 2023Management of late blight of potato incited by Phytophthora infestans remains a major challenge. Coevolution of pathogen with resistant strains and the rise of fungicide...
Management of late blight of potato incited by Phytophthora infestans remains a major challenge. Coevolution of pathogen with resistant strains and the rise of fungicide resistance have made it more challenging to prevent the spread of P. infestans. Here, the anti-oomycete potential of Bacillus velezensis VB7 against P. infestans through pan-genome analysis and molecular docking were explored. The Biocontrol potential of VB7 against P. infestans was assessed using a confrontational assay. The biomolecules from the inhibition zone were identified and subjected to in silico analysis against P. infestans target proteins. Nucleotide sequences for 54 B. velezensis strains from different geographical locations were used for pan-genome analysis. The confrontational assay revealed the anti-oomycetes potential of VB7 against P. infestans. Molecular docking confirmed that the penicillamine disulfide had the maximum binding energy with eight effector proteins of P. infestans. Besides, scanning electron microscopic observations of P. infestans interaction with VB7 revealed structural changes in hypha and sporangia. Pan-genome analysis between 54 strains of B. velezensis confirmed that the core genome had 2226 genes, and it has an open pan-genome. The present study confirmed the anti-oomycete potential of B. velezensis VB7 against P. infestans and paved the way to explore the genetic potential of VB7.
Topics: Phytophthora infestans; Molecular Docking Simulation; Solanum tuberosum; Base Sequence; Plant Diseases
PubMed: 36577205
DOI: 10.1016/j.micres.2022.127277 -
Molecules (Basel, Switzerland) Dec 2022Glioblastoma multiforme (GBM) is a fast-growing and aggressive type of brain cancer. Unlike normal brain cells, GBM cells exhibit epithelial-mesenchymal transition...
Glioblastoma multiforme (GBM) is a fast-growing and aggressive type of brain cancer. Unlike normal brain cells, GBM cells exhibit epithelial-mesenchymal transition (EMT), which is a crucial biological process in embryonic development and cell metastasis, and are highly invasive. Copper reportedly plays a critical role in the progression of a variety of cancers, including brain, breast, and lung cancers. However, excessive copper is toxic to cells. D-penicillamine (DPA) and triethylenetetramine (TETA) are well-known copper chelators and are the mainstay of treatment for copper-associated diseases. Following treatment with copper sulfate and DPA, GBM cells showed inhibition of proliferation and suppression of EMT properties, including reduced expression levels of N-cadherin, E-cadherin, and Zeb, which are cell markers associated with EMT. In contrast, treatment with copper sulfate and TETA yielded the opposite effects in GBM. Genes, including , are associated with an increase in copper levels, implying their role in EMT. To analyze the invasion and spread of GBM, we used zebrafish embryos xenografted with the GBM cell line U87. The invasion of GBM cells into zebrafish embryos was markedly inhibited by copper treatment with DPA. Our findings suggest that treatment with copper and DPA inhibits proliferation and EMT through a mechanism involving TGF-β/Smad signaling in GBM. Therefore, DPA, but not TETA, could be used as adjuvant therapy for GBM with high copper concentrations.
Topics: Animals; Glioblastoma; Copper; Zebrafish; Cell Line, Tumor; Copper Sulfate; Brain Neoplasms; Signal Transduction; Transforming Growth Factor beta; Chelating Agents; Epithelial-Mesenchymal Transition; Cell Movement
PubMed: 36557987
DOI: 10.3390/molecules27248851 -
Journal of Yeungnam Medical Science Jul 2023Thallium poisoning is usually accidental. We present a case of a 51-year-old woman who was evaluated in June 2018 for myalgia, vertigo, asthenia, and abdominal pain....
Thallium poisoning is usually accidental. We present a case of a 51-year-old woman who was evaluated in June 2018 for myalgia, vertigo, asthenia, and abdominal pain. Physical examination revealed temporal-spatial disorientation, jaundice, and asterixis. The laboratory reported the following: bilirubin, 10.3 mg/dL; aspartate transaminase, 78 U/L; alanine transaminase, 194 U/L; albumin, 2.3 g/dL; prothrombin time, 40%; and platelet count, 60,000/mm3. Serology performed for hepatitis A, B, and C; Epstein-Barr virus; cytomegalovirus; and human immunodeficiency virus was negative, and a collagenogram was negative. Physical reevaluation revealed alopecia on the scalp, armpits, and eyebrows; macules on the face; plantar hyperkeratosis; and ulcers on the lower limbs. Tests for lead, arsenic, copper, and mercury were carried out, which were normal; however, elevated urinary thallium (540 µg/g; range, 0.4-10 µg/g) was observed. The patient was treated with ᴅ-penicillamine 1,000 mg/day and recovered her urinary thallium levels were within normal range at annual follow-up. Thallium poisoning is extremely rare and can be fatal in small doses. An adequate clinical approach can facilitate early diagnosis.
PubMed: 36537175
DOI: 10.12701/jyms.2022.00647 -
Biomedicine & Pharmacotherapy =... Feb 2023There are considerable evidence of reproductive impairment in male organisms with Wilson disease (WD). The purpose of this study was to observe spermatogenesis,...
Glutathione improves testicular spermatogenesis through inhibiting oxidative stress, mitochondrial damage, and apoptosis induced by copper deposition in mice with Wilson disease.
BACKGROUND AND OBJECTIVE
There are considerable evidence of reproductive impairment in male organisms with Wilson disease (WD). The purpose of this study was to observe spermatogenesis, mitochondrial damage, apoptosis, and the level of oxidative stress in the testes of Wilson disease model TX mice, and to observe the effect and mechanism of glutathione on testicular spermatogenesis.
METHODS
Mice were divided into a normal control group (control group), Wilson disease model TX mice group (WD group), penicillamine-treated TX mice group (penicillamine group) and glutathione-treated TX mice group (glutathione group). Testicular coefficient, histomorphology of testis and epididymis, number of spermatozoa, apoptosis of spermatogenic cells and expression of apoptosis-related proteins were observed. Ultrastructural analysis of mitochondria and mitochondrial membrane potential (MMP) monitored using JC-1 dye were used to detect mitochondrial damage. The levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and reactive oxygen species (ROS) in testicular cells were measured to assess oxidative stress.
RESULTS
Testicular coefficient did not change in mice with Wilson disease. However, the tissue structure of the testicular seminiferous tubules was damaged, and the number of spermatozoa in the epididymal lumen was significantly reduced in WD group. The apoptosis rate in the testes was significantly increased. The protein expression of the pro-apoptotic proteins Bax and Caspase-3 significantly increased, and the expressions of the anti-apoptotic protein Bcl-2 significantly decreased. The levels of ROS and MDA significantly increased, and the levels of CAT and GSH significantly decreased. Mitochondria with abnormal ultrastructure and the rate of JC-1 positive cells were significantly increased in the WD group. After copper chelation by penicillamine, the structure of the testicular seminiferous tubules and the number of spermatozoa in the epididymal lumen were significantly improved. The number of apoptotic cells was significantly reduced. The levels of Bax and Caspase-3 decreased, and the expression of Bcl-2 increased. The contents of CAT and GSH increased, and the levels of ROS and MDA decreased significantly. The abnormal mitochondria and JC-1 positive cells was significantly decreased. The histomorphology of seminiferous tubules, spermatogenic function, apoptosis rate, apoptosis-related proteins, mitochondrial damage, and oxidative stress in Wilson disease TX mice significantly improved after glutathione treatment.
CONCLUSION
Copper deposition in Wilson disease can lead to oxidative stress injury, mitochondrial damage, and apoptosis in the testis, leading to the impairment of spermatogenesis. Glutathione may improve testicular spermatogenesis in male Wilson disease TX mice by inhibiting copper deposition-induced oxidative stress, mitochondrial damage, and apoptosis.
Topics: Mice; Male; Animals; Testis; Copper; Caspase 3; Reactive Oxygen Species; Hepatolenticular Degeneration; bcl-2-Associated X Protein; Spermatogenesis; Oxidative Stress; Apoptosis; Glutathione; Apoptosis Regulatory Proteins; Penicillamine
PubMed: 36502753
DOI: 10.1016/j.biopha.2022.114107 -
Scientific Reports Dec 2022Smoke emissions produced by firearms contain hazardous chemicals, but little is known if their properties change depending on firearm and ammunition type and whether...
Smoke emissions produced by firearms contain hazardous chemicals, but little is known if their properties change depending on firearm and ammunition type and whether such changes affect toxicity outcomes. Pulmonary toxicity was assessed in mice exposed by oropharyngeal aspiration to six different types of smoke-related particulate matter (PM) samples; (1) handgun PM, (2) rifle PM, (3) copper (Cu) particles (a surrogate for Cu in the rifle PM) with and without the Cu chelator penicillamine, (4) water-soluble components of the rifle PM, (5) soluble components with removal of metal ions, and (6) insoluble components of the rifle PM. Gun firing smoke PM was in the respirable size range but the chemical composition varied with high levels of Pb in the handgun and Cu in the rifle smoke. The handgun PM did not induce appreciable lung toxicity at 4 and 24 h post-exposure while the rifle PM significantly increased lung inflammation and reduced lung function. The same levels of pure Cu particles alone and the soluble components from the rifle fire PM increased neutrophil numbers but did not cause appreciable cellular damage or lung function changes when compared to the negative (saline) control. Penicillamine treated rifle PM or Cu, slightly reduced lung inflammation and injury but did not improve the lung function decrements. Chelation of the soluble metal ions from the rifle fire PM neutralized the lung toxicity while the insoluble components induced the lung toxicity to the same degree as the rifle PM. The results show that different firearm types can generate contrasting chemical spectra in their emissions and that the rifle PM effects were mostly driven by water-insoluble components containing high levels of Cu. These findings provide better knowledge of hazardous substances in gun firing smoke and their potential toxicological profile.
Topics: Animals; Mice; Particulate Matter; Firearms; Penicillamine; Hazardous Substances; Chelating Agents; Water; Lung
PubMed: 36456643
DOI: 10.1038/s41598-022-24856-5 -
Frontiers in Behavioral Neuroscience 2022Early ontogeny of the rat (late gestation and postnatal first week) is a sensitive period to ethanol's positive reinforcing effects and its detrimental effects on...
Moderate ethanol exposure during early ontogeny of the rat alters respiratory plasticity, ultrasonic distress vocalizations, increases brain catalase activity, and acetaldehyde-mediated ethanol intake.
Early ontogeny of the rat (late gestation and postnatal first week) is a sensitive period to ethanol's positive reinforcing effects and its detrimental effects on respiratory plasticity. Recent studies show that acetaldehyde, the first ethanol metabolite, plays a key role in the modulation of ethanol motivational effects. Ethanol brain metabolization into acetaldehyde via the catalase system appears critical in modulating ethanol positive reinforcing consequences. Catalase system activity peak levels occur early in the ontogeny. Yet, the role of ethanol-derived acetaldehyde during the late gestational period on respiration response, ultrasonic vocalizations (USVs), and ethanol intake during the first week of the rat remains poorly explored. In the present study, pregnant rats were given a subcutaneous injection of an acetaldehyde-sequestering agent (D-penicillamine, 50 mg/kg) or saline (0.9% NaCl), 30 min prior to an intragastric administration of ethanol (2.0 g/kg) or water (vehicle) on gestational days 17-20. Respiration rates (breaths/min) and apneic episodes in a whole-body plethysmograph were registered on postnatal days (PDs) 2 and 4, while simultaneously pups received milk or ethanol infusions for 40-min in an artificial lactation test. Each intake test was followed by a 5-min long USVs emission record. On PD 8, immediately after pups completed a 15-min ethanol intake test, brain samples were collected and kept frozen for catalase activity determination. Results indicated that a moderate experience with ethanol during the late gestational period disrupted breathing plasticity, increased ethanol intake, as well brain catalase activity. Animals postnatally exposed to ethanol increased their ethanol intake and exerted differential affective reactions on USVs and apneic episodes depending on whether the experience with ethanol occur prenatal or postnatally. Under the present experimental conditions, we failed to observe, a clear role of acetaldehyde mediating ethanol's effects on respiratory plasticity or affective states, nevertheless gestational acetaldehyde was of crucial importance in determining subsequent ethanol intake affinity. As a whole, results emphasize the importance of considering the participation of acetaldehyde in fetal programming processes derived from a brief moderate ethanol experience early in development, which in turn, argues against "safe or harmless" ethanol levels of exposure.
PubMed: 36439967
DOI: 10.3389/fnbeh.2022.1031115 -
Biomolecules Nov 2022The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead... (Review)
Review
The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox-DFOA and the tetrathiomolybdate-DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations.
Topics: Humans; Manganese; Copper; Iron; Chelating Agents; Ions; Metals; Neurotoxicity Syndromes; Succimer; Water
PubMed: 36421727
DOI: 10.3390/biom12111713 -
International Journal of Women's... Dec 2022
PubMed: 36415850
DOI: 10.1097/JW9.0000000000000058