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Inhibition of MALAT1 facilitates ROS accumulation via the Keap1/HO-1 pathway to enhance photodynamic therapy in secondary hyperparathyroidism.

The prevalence of secondary hyperparathyroidism (SHPT) in advanced chronic kidney disease (CKD) exceeds 80 %. Our previous study indicated that photodynamic therapy (PDT) has potential for treating SHPT. Long noncoding RNA (lncRNA) is involved in various oxidative stress and apoptotic processes, but the molecular mechanism remains unreported. In this study, we found that PDT induced apoptosis in SHPT through reactive oxygen species (ROS) accumulation. The expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and heme oxygenase 1 (HO-1) within SHPT was upregulated after

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… CQ, chloroquine; CHX, cycloheximide; NC, non-specific control. ∗∗P < 0.01; ∗∗∗P < 0.001; ns, no significance. … Fig. 7 Moreover, we utilized chloroquine (CQ) and MG132 to inhibit degradation of Keap1 protein by two pathways: the autophagy-lysosome and ubiquitin-proteasome dependent degradation pathways, respectively [ [30] , [31] , [32] ]. …

Emerging therapeutics in the management of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We

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… On March 28, 2020 the United States Federal Drug Administration (FDA) issued an emergency authorization for chloroquine (CQ) phosphate and hydroxychloroquine (HCQ) sulfate as a treatment for adults and adolescents weighing greater than 50 kg, who are hospitalized, and for whom a clinical trial is not … Drug | Current use/FDA approval | Proposed mechanism of action | Published trials APN01 | Known to have anti-hypertensive and anti-neoplastic properties | Cleaves angiotensin II to form angiotensin-1-7 | See Clinicaltrials.gov for ongoing trials Chloroquine/hydroxychloroquine | Anti-malarial, anti-viral …

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

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… | NCT01023477 (phase I/II): testing whether chloroquine reduces the ability of ductal carcinoma in situ to survive and spread. … Chloroquine-induced inhibition of STAT3 signaling as a mechanism for the anti-CSC activity of chloroquine has been reported also by Choi et al. ( 185 ). Chloroquine is currently being investigated in clinical studies for its anti-CSC activity (see Table 5 ). …

Current Status of COVID-19 Therapies and Drug Repositioning Applications.

The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in dru

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… A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 J. Crit. Care 57 2020 279 283 32173110 10.1016/j.jcrc.2020.03.005 PMC7270792 De Clercq E. Li G. Approved antiviral drugs over the past 50 years Clin. Microbiol. … Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Cell Res. 30 2020 269 271 32020029 10.1038/s41422-020-0282-0 PMC7054408 Wang Y. Wang Y. Chen Y. Qin Q. …

Role of autophagy in cholangiocarcinoma: Pathophysiology and implications for therapy.

Cholangiocarcinoma (CCA) is a malignant tumour of the biliary system that originates from the neoplastic transformation of cholangiocytes. CCA is characterized by late diagnosis and poor outcome, with surgery considered as the last option for management. Autophagy is a physiological lysosomal degradation process, essential for cellular homeostasis and ubiquitous in all eukaryotic cells. Several studies have reported a potential involvement of autophagy in cancer, but it remains unclear whether activation of this process represents a survival mechanism of cancer cells. In the present review, we

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… Olaparib has been shown to induce autophagy in ovarian cancer cells, and autophagy provides an adaptive mechanism of PARP inhibitor resistance that can be overcome, as confirmed by inhibition of autophagy, with chloroquine, hydroxychloroquine, and LYS05. … Furthermore, chloroquine reduced the viability of QBC939 cells, due to the accumulation of large quantities of protein in the cytoplasm leading to endoplasmic reticulum stress and cellular apoptosis[ 31 ]. …

Autophagy in the physiological endometrium and cancer.

Autophagy is a highly conserved catabolic process and a major cellular pathway for the degradation of long-lived proteins and cytoplasmic or … inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; CMA: chaperone-mediated autophagy; CQ: chloroquine; CTNNB1: catenin beta 1; DDIT3: DNA damage inducible transcript 3; EC: endometrial cancer; EGFR: epidermal growth factor receptor; EH: endometrial hyperplasia; EIF4E: eukaryotic translation initiation factor 4E; EPHB2/ERK: EPH receptor B2; ER: endop …

Glucose controls metallothionein 1 gene expression in pancreatic islets via a mechanism involving cellular metabolism, granular zinc and the zinc transporter ZnT8 in rat and mouse.

AIMS/HYPOTHESIS: Metallothionein 1 (MT1) negatively regulates insulin secretion in pancreatic beta cells, and is upregulated by low non-stim … ement, islet cells cultured in G2 vs G10 medium showed an increase in [Zn2+]c that was prevented by chloroquine treatment. Co-staining with nuclear and cytosolic markers confirmed the cytosolic and perinuclear subcellular localisation of increased [Zn2+]c in G2 medium. This effect was reproduced in MIN6 cells cultured in G5 vs G25 medium (containing 25 mmol/l …

Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute.

ObjectiveThis study aimed to describe the demographic and clinical characteristics of cancer inpatients with COVID-19 exploring clinical outcomes.MethodsA retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR.ResultsThe mean age was 55.3 years (SD ± 21.1). Comorbidities were present in 110 (60.8%) cases. The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22

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… Eight (4.4%) patients received chloroquine and 36 (19.9%), ivermectin. At the time of analysis, a total of 60 patients (33.1%) had died due to COVID-19. … Also, specific therapies during the COVID-19 course, such as oseltamivir, therapeutic anticoagulation, corticosteroids, ivermectin and chloroquine did not influence the risk of death ( S2 Table ). …

Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy.

Cholangiocarcinomas (CCAs) are diverse biliary epithelial tumours involving the intrahepatic, perihilar and distal parts of the biliary tree. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis and strategy for clinical management. However, many cholangiocarcinoma tumor-cells appear to be resistant to current chemotherapeutic agents. The role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in CCA. The multistep nature of autophagy offers a plethora of regulation points, which are prone to be deregulated and

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… The utilization of chloroquine (CQ) ceased tumor growth via the inhibition of the mechanism, resulting in the accumulation of LC3-II[ 42 ]. … Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS. PLoS One. 2017;12:e0173712. doi: 10.1371/journal.pone.0173712. 80. Isomoto H. …

Pharmacological treatments of COVID-19.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and

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… associated protein kinase 1 (AAK1) that promotes endocytosis of the virus, (b) interaction with cyclin G-associated kinase (GAK); anti-inflammatory | [ 153 – 155 ] Ruxolitinib | Janus kinase (JAK) enzymes | Prevents viral entry into cells by inhibiting the viral clathrin-mediated endocytosis | [ 157 , 161 ] Chloroquine … Inhibitors of viral entry to the host cell Chloroquine/hydroxychloroquine The sulfate and phosphate salts of chloroquine (CQ) are categorized as anti-malarial drugs. …

Role of phytoconstituents in the management of COVID-19.

BackgroundCOVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas.Scope and approachThis review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry

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… Camostat mesylate Serine protease inhibitor TMPRSS2 Under phase 1 and 2 of clinical trials [ 73 ] Nafamostat mesylate Serine protease inhibitor TMPRSS2 Under phase 2 and 3 of clinical trials [ 73 ] Chloroquine phosphate Antimalarial ACE-2 Under phase 2 of clinical trials [ 73 ] Hydroxy-chloroquine Antimalarial … Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Cell Discovery 6 2020 16 10.1038/s41421-020-0156-0 32194981 PMC7078228 61 Zhang J. Xie B. Hashimoto K. …

Bisphosphonates for the Treatment of Calcinosis Cutis-A Retrospective Single-Center Study.

(1) Background: Calcinosis cutis is a frequent symptom of autoimmune connective tissue diseases leading to pain, transcutaneous expulsion of calcified material and bacterial superinfection. There is a high need for new therapeutic options as no standardized treatment algorithm is established. While case reports indicate beneficial effects of bisphosphonates, standardized evaluation of treatment effects is missing. (2) Methods: In this retrospective analysis we evaluate the effects of intravenous pamidronate, a second-generation bisphosphonate, in seven patients with calcinosis cutis using cons

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… bisphospho-nate cycles | 7 | 12 | 3 | 6 | 12 | 18 | 2 dosage (mg) | 70 | 75 | 75 | 75 | 75 | 75 | 75 previous treatments | intravenous immuno-globulins cyclophosphamid methyl-prednisolone azathioprine | methotrexate prednisolone azathioprine | intravenous immuno-globuline methotrexate prednisolone azathioprine chloroquine … PUVA, iloprost | methotrexate prednisolone cyclosporine chloroquine | bosentan pentoxi-fylline | hydroxy-chloroquine azathioprin mycophenolate mofetil intravenous immuno-globulins prednisolone iloprost | prednisolone treatment during bisphospho-nate therapy | methyl-prednisolone | methotrexate prednisolone …

Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: To assess the efficacy of ivermectin in addition to standard treatment compared to standard treatment alone in reducing hospital … at the time of admission for another viral pathology other than COVID-19; (9) need or use of hydroxychloroquine or chloroquine; (10) use of ivermectin up to 7 days prior to randomization; (11) patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months; and (12) current participation or in the last 30 days in a …

Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.

Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper th

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… (Hydroxy-) Chloroquine Huge efforts have been taken to systematically screen existing drug libraries in order to find treatments for COVID-19 ( 76 ). … Chloroquine is a Potent Inhibitor of SARS Coronavirus Infection and Spread . Virol J ( 2005 ) 2 : 69 . doi: 10.1186/1743-422X-2-69 16115318 PMC1232869 81 Yao X Ye F Zhang M Cui C Huang B Niu P . …

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

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… Thomas et al. reported that chloroquine further increased the cytotoxicity of dual treatment of nelfinavir and DMC selectively in TNBC cells [ 41 ]. … AMPK leads to inhibition of mTOR and activates autophagy at the downstream level, facilitating synergism between nelfinavir and autophagy inhibitors, such as chloroquine [ 69 ]. …

Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

Despite effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. Analysis of RNA sequencing data from CD138 + MM patient cells (n = 813) across disease stages identifies an autophagy gene signature. Particularly elevated ULK3 expression is strongly associated with disease progression. Functional studies reveal that ULK3 supports MM cell survival via the ULK-ATG13-FIP200 complex. We generate small-molecule kinase inhibitors (SG3-014/MA9-060) exhibiting nanomolar potency against ULK3, with binding confirmed by co-crystallization. While ex

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… Chloroquine (CQ) (1 µM) served as a positive control for autophagy inhibition. … Chloroquine (CQ) (1 µM) served as a positive control for autophagy inhibition. …

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines a

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… In conclusion, while specific antiviral therapies are in rapid development (remdesivir, chloroquine, vaccine), controlling the powerful inflammatory response causing severe IP or ARDS is a reasonable approach. … Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro . Cell Res. (2020) 30:269–71. 10.1038/s41422-020-0282-0 31. Gao J, Tian Z, Yang X. …

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview.

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans. The overwhelming outbreak of SARS-CoV-2 continues to unfold all over the world, urging scientists to put an end to this global pandemic through biological and

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… Chloroquine and Hydroxychloroquine It is a racemic combination of two enantiomers, R and S. Hydroxychloroquine, like chloroquine, is an aminoquinoline [ 145 ]. … A chloroquine derivative with a hydroxyl group, hydroxychloroquine possesses chloroquine-like pharmacokinetics, quick gastrointestinal absorption, and renal excretion, as well as a less dangerous profile [ 147 ]. …

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.

Protein quality control allows eukaryotes to maintain proteostasis under the stress of constantly changing conditions. In this review, we discuss the current literature on PQC, highlighting flaws that must exist for malignancy to occur. At the nidus of PQC, the expression of BAG1-6 reflects the cell environment; each isoform directs proteins toward different, parallel branches of the quality control cascade. The sum of these branches creates a net shift toward either homeostasis or apoptosis. With an established role in ALP, Bag3 is necessary for cell survival in stress conditions including th

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… The combination chloroquine/hydroxychloroquine, which was first FDA-approved for its anti-malarial properties, inhibits the fusion of the autophagosome and the lysosome [ 146 ]. … Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine Neurosurg. Focus 2003 14 e3 10.3171/foc.2003.14.2.4 15727424 143. Sotelo J. Briceño E. López-González M.A. …

Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between the proteasome, autophagy, and reactive oxygen species (ROS) have been shown in the past, thus emphasizing the need for a better understanding of the underlying pathophysiology. For this study, bone marrow mononuclear cells from 110 myeloma patients were collected at different disease stages. PSMB5 and LC3I/II protein levels were determined using Western blot, proteasome proteolytic activity (PPA) with spectrofluorometry, and ROS with flow cytometry. PSMB5 accumulation

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… They also demonstrated that inhibitors of autophagy, such as chloroquine, when co-administered with Bortezomib, can overcome autophagy-mediated Bortezomib resistance [ 81 ]. … Chloroquine and Hydroxychloroquine Toxicity StatPearls StatPearls Publishing Treasure Island, FL, USA 2024 30725771 …