Accidental methotrexate overdose leading to multisystem toxicity: A case report.

Background: Methotrexate (MTX) is an extensively used chemotherapeutic agent with well-characterized toxicity profiles. This case report describes the clinical presentation, management, and outcome of a patient presenting with severe MTX toxicity.

Case Presentation: A 35-year-old Bangladeshi female was admitted on March 9, 2024, with severe mucosal ulcerations, painful skin lesions, and gastrointestinal bleeding after ingesting Methotrexate daily for 12 days by mistake instead of the medication prescribed to her.

Paraquat induced acute kidney and lung injury with a dramatic response to methylprednisolone: A case report.

Background: Paraquat poisoning is one of the leading causes of fatal poisoning in many parts of the world, especially in agricultural countries. Its high toxicity even in small amounts causes rapid damage to multiple organs, especially the kidneys, lungs, and liver, mainly through free radical-mediated injury. As no specific antidote is yet available, early diagnosis and the importance of supportive therapy are critical parts of management.

Psychosocial Factors Behind Deliberate Self-Poisoning in a Tertiary Care Hospital of Bangladesh: A Cross-Sectional Study.

Introduction: Deliberate self-poisoning (DSP) is an important cause of hospital admissions and subsequent mortality. We conducted a cross-sectional observational study in a tertiary-level teaching hospital situated in the northeastern part of Bangladesh to analyze the psychosocial factors responsible for DSP.

Methods: This cross-sectional observational study was carried out among patients with DSP admitted to the medicine ward from January to December 2017, irrespective of gender, except for cases involving poisoning due to spoiled food, food contaminated by infectious organisms, poisoning by venomous animals, and street poisoning (commuter or travel-related poisoning).

COVID-19 mRNA vaccine-associated encephalopathy, myocarditis, and thrombocytopenia with excellent response to methylprednisolone: A case report.

Introduction: Large-scale vaccination is considered one of the most effective strategies to control the pandemic of COVID-19. Since its start, different complications have been described thought to be related to vaccination. Here, we present a rare case where encephalopathy, myocarditis, and thrombocytopenia developed simultaneously following the second dose of Pfizer-BioNTech mRNA vaccine (BNT162b2).

Paraquat-induced acute kidney and liver injury: Case report of a survivor from Bangladesh.

Despite high fatality following paraquat ingestion, a few percentages of patients survive even after organ damage appears. We need to focus more on careful clinical and laboratory monitoring. Early diagnosis and Supportive therapy are crucial.

Adeno-Associated Virus Vector-Mediated Expression of Antirespiratory Syncytial Virus Antibody Prevents Infection in Mouse Airways.

Infants and older adults are especially vulnerable to infection by respiratory syncytial virus (RSV), which can cause significant illness and irreparable damage to the lower respiratory tract and for which an effective vaccine is not readily available. Palivizumab, a recombinant monoclonal antibody (mAb), is an approved therapeutic for RSV infection for use in high-risk infants only. Due to several logistical issues, including cost of goods and scale-up limitations, palivizumab is not approved for other populations that are vulnerable to severe RSV infections, such as older adults.

Context-Specific Function of the Engineered Peptide Domain of PHP.B.

One approach to improve the utility of adeno-associated virus (AAV)-based gene therapy is to engineer the AAV capsid to (i) overcome poor transport through tissue barriers and (ii) redirect the broadly tropic AAV to disease-relevant cell types. Peptide- or protein-domain insertions into AAV surface loops can achieve both engineering goals by introducing a new interaction surface on the AAV capsid. However, we understand little about the impact of insertions on capsid structure and the extent to which engineered inserts depend on a specific capsid context to function.

αvβ3 Integrin Is Required for Efficient Infection of Epithelial Cells with Human Adenovirus Type 26.

Human adenoviruses (HAdVs) are being explored as vectors for gene transfer and vaccination. Human adenovirus type 26 (HAdV26), which belongs to the largest subgroup of adenoviruses, species D, has a short fiber and a so-far-unknown natural tropism. Due to its low seroprevalence, HAdV26 has been considered a promising vector for the development of vaccines.

An indirect watermark hiding in discrete cosine transform-singular value decomposition domain for copyright protection.

Digital image watermarking has emerged as a promising solution for copyright protection. In this paper, a discrete cosine transform (DCT) and singular value decomposition (SVD) based hybrid robust image watermarking method using Arnold scrambling is proposed and simulated to protect the copyright of natural images. In this proposed scheme, before embedding, watermark is scrambled with Arnold scrambling.

Optogenetic control of mitochondrial metabolism and Ca signaling by mitochondria-targeted opsins.

Key mitochondrial functions such as ATP production, Ca uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH) across the inner membrane. Although several drugs can modulate ΔμH, their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control.

Mitochondria control store-operated Ca entry through Na and redox signals.

Mitochondria exert important control over plasma membrane (PM) Orai1 channels mediating store-operated Ca entry (SOCE). Although the sensing of endoplasmic reticulum (ER) Ca stores by STIM proteins and coupling to Orai1 channels is well understood, how mitochondria communicate with Orai1 channels to regulate SOCE activation remains elusive. Here, we reveal that SOCE is accompanied by a rise in cytosolic Na that is critical in activating the mitochondrial Na/Ca exchanger (NCLX) causing enhanced mitochondrial Na uptake and Ca efflux.

The NCLX-type Na/Ca Exchanger NCX-9 Is Required for Patterning of Neural Circuits in .

NCLX is a Na/Ca exchanger that uses energy stored in the transmembrane sodium gradient to facilitate the exchange of sodium ions for ionic calcium. Mammals have a single NCLX, which has been shown to function primarily at the mitochondrion and is an important regulator of neuronal physiology by contributing to neurotransmission and synaptic plasticity. The role of NCLX in developmental cell patterning ( in neural circuits) is largely unknown.

Identification of residues that control Li versus Na dependent Ca exchange at the transport site of the mitochondrial NCLX.

Background: The Na/Ca/Li exchanger (NCLX) is a member of the Na/Ca exchanger family. NCLX is unique in its capacity to transport both Na and Li, unlike other members, which are Na selective. The major aim of this study was twofold, i.

Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques.

The seroprevalence of neutralizing antibodies (NAbs) to adeno-associated viral (AAV) vector capsids may preclude a percentage of the population from receiving gene therapy, particularly following systemic vector administration. We hypothesized that the use of intramuscular (IM) administration of AAV vectors might circumvent this issue. IM injections were used to administer AAV8 vectors expressing either secreted or non-secreted transgenes into mice and the influence of NAbs supplied by pre-administration of pooled human IgG on transgene expression was evaluated.

Recombinant measles virus incorporating heterologous viral membrane proteins for use as vaccines.

Recombinant measles virus (rMV) vectors expressing heterologous viral membrane protein antigens are potentially useful as vaccines. Genes encoding the mumps virus haemagglutinin-neuraminidase (MuV-HN), the influenza virus haemagglutinin (Flu-HA) or the respiratory syncytial virus fusion (RSV-F) proteins were inserted into the genome of a live attenuated vaccine strain of measles virus. Additionally, in this case rMV with the MuV-HN or the influenza HA inserts, chimeric constructs were created that harboured the measles virus native haemagglutinin or fusion protein cytoplasmic domains.

Intramuscular injection of AAV8 in mice and macaques is associated with substantial hepatic targeting and transgene expression.

Intramuscular (IM) administration of adeno-associated viral (AAV) vectors has entered the early stages of clinical development with some success, including the first approved gene therapy product in the West called Glybera. In preparation for broader clinical development of IM AAV vector gene therapy, we conducted detailed pre-clinical studies in mice and macaques evaluating aspects of delivery that could affect performance. We found that following IM administration of AAV8 vectors in mice, a portion of the vector reached the liver and hepatic gene expression contributed significantly to total expression of secreted transgenes.

Adeno-associated virus 9-mediated airway expression of antibody protects old and immunodeficient mice against influenza virus.

Influenza causes serious and sometimes fatal disease in individuals at risk due to advanced age or immunodeficiencies. Despite progress in the development of seasonal influenza vaccines, vaccine efficacy in elderly and immunocompromised individuals remains low. We recently developed a passive immunization strategy using an adeno-associated virus (AAV) vector to deliver a neutralizing anti-influenza antibody at the site of infection, the nasal airways.

Increased mucosal CD4+ T cell activation in rhesus macaques following vaccination with an adenoviral vector.

Unlabelled: The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques.

Role of PKC-ζ in NADPH oxidase-PKCα-Giα axis dependent inhibition of β-adrenergic response by U46619 in pulmonary artery smooth muscle cells.

Treatment of bovine pulmonary artery smooth muscle cells (BPASMCs) with U46619 attenuated isoproterenol caused stimulation of adenyl cyclase activity and cAMP production. Pretreatment with SQ29548 (Tp receptor antagonist), apocynin (NADPH oxidase inhibitor) and Go6976 (PKC-α inhibitor) eliminated U46619 caused attenuation of isoproterenol stimulated adenyl cyclase activity. Pretreatment with SQ29548 and apocynin prevented U46619 induced increase in NADPH oxidase activity, PKC-α activity and Giα phosphorylation.

Activation of proMMP-2 by U46619 occurs via involvement of p(38)MAPK-NFκB-MT1MMP signaling pathway in pulmonary artery smooth muscle cells.

We investigated the mechanism by which TxA2 mimetic, U46619, activates proMMP-2 in bovine pulmonary artery smooth muscle cells. Our study showed that treatment of the cells with U46619 caused an increase in the expression and subsequently activation of proMMP-2 in the cells. Pretreatment with p(38)MAPK inhibitor, SB203580; and NF-κB inhibitor, Bay11-7082 inhibited the expression and activation of proMMP-2 induced by U46619.

Role of PKC-α in NF-κB-MT1-MMP-mediated activation of proMMP-2 by TNF-α in pulmonary artery smooth muscle cells.

We sought to evaluate the mechanism(s) associated with pro matrix metalloprotease 2 (proMMP-2) activation in bovine pulmonary artery smooth muscle cells. Preincubation of cells with anti-TNFR1 antibody prevented tumour necrosis factor-α (TNF-α)-induced proMMP-2 activation and increase in membrane type 1 matrix metalloprotease (MT1-MMP) expression as well as inhibition of tissue inhibitor of metalloproteinase 2 (TIMP-2) expression, indicating the role of TNFR1 receptor during TNF-α stimulation. Anti-MT1-MMP antibody abrogated proMMP-2 activation by TNF-α-stimulated cell membrane, suggesting the involvement of MT1-MMP in proMMP-2 activation.

Role of PKCα-p38 MAPK-Giα axis in peroxynitrite-mediated inhibition of β-adrenergic response in pulmonary artery smooth muscle cells.

In the context of cross-talk between transmembrane signaling pathways, we studied the loci within the β-adrenergic receptor/G protein/adenyl cyclase system at which PKC exerts regulatory effects of peroxynitrite (ONOO(-)) on isoproterenol stimulated adenyl cyclase activity in pulmonary artery smooth muscle cells. Treatment of the cells with ONOO(-) stimulated PKC-α activity and that subsequently increased p(38)MAPK phosphorylation. Pretreatment with Go6976 (PKC-α inhibitor) and SB203580 (p(38)MAPK inhibitor) eliminated ONOO(-) caused inhibition on isoproterenol stimulated adenyl cyclase activity.

Adenoviruses in fecal samples from asymptomatic rhesus macaques, United States.

Adenoviruses can cause infectious diarrheal disease or respiratory infections in humans; 2 recent reports have indicated probable human infection with simian adenoviruses (SAdVs). To assess the possibility of animal-to-human transmission of SAdVs, we tested fecal samples from asymptomatic rhesus macaques housed in 5 primate facilities in the United States and cultured 23 SAdV isolates. Of these, 9 were purified and completely sequenced; 3 SAdV samples from the American Type Culture Collection (SAdV-6, SAdV-18, and SAdV-20) were also completely sequenced.

Role of PKCα-p(38)MAPK-G(i)α axis in NADPH oxidase derived O(2)(·-)-mediated activation of cPLA(2) under U46619 stimulation in pulmonary artery smooth muscle cells.

We have recently reported that treatment of bovine pulmonary artery smooth muscle cells with the thromboxane A(2) mimetic, U46619 stimulated NADPH oxidase derived O(2)(·-) level, which subsequently caused marked increase in [Ca(2+)](i)[17]. Herein, we demonstrated that O(2)(·-)-mediated increase in [Ca(2+)](i) stimulates an aprotinin sensitive proteinase activity, which proteolytically activates PKC-α under U46619 treatment to the cells. The activated PKC-α then phosphorylates p(38)MAPK and that subsequently caused G(i)α phosphorylation leading to stimulation of cPLA(2) activity in the cell membrane.