scholarly journals Screening of Botanical Drugs against SARS-CoV-2 Entry

2021 ◽  
Author(s):  
Junyuan Cao ◽  
Yang Liu ◽  
Minmin Zhou ◽  
Siqi Dong ◽  
Xiaoying Jia ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Treatment Options ◽  
Specific Treatment ◽  
Mechanistic Study ◽  
Schisandrin B ◽  
The Novel ◽  
Effective Inhibition ◽  
Botanical Drug ◽  
Oleanonic Acid ◽  
Combination Studies

An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacting global health. Specific treatment options for diseases caused by SARS-CoV-2 are largely lacking. Herein, we used a pseudotype virus (pv) bearing the SARS-CoV-2 S glycoprotein to screen a botanical drug library to identify an agent against SARS-CoV-2 entry. All the four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, were identified for effective inhibition of SARS-CoV-2 S pv entry in the micromolar range. A mechanistic study revealed that these four agents inhibit SARS-CoV-2 S pv entry by blocking S-mediated membrane fusion. Furthermore, angeloylgomisin O, schisandrin B, and oleanonic acid inhibited authentic SARS-CoV-2 with a high selective index (SI). We also showed that all the four hits could also inhibit the entry of pv of Middle East respiratory syndrome coronavirus (MERS-CoV) and newly emerged SARS-CoV-2 variants (D614G, K417N/E484K/N501Y/D614G). In drug combination studies performed in cellular antiviral assays, angeloylgomisin O and schisandrin B displayed synergistic effects in combination with remdesivir. These results indicated that angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid can inhibit SARS-CoV-2 and that they are potential therapeutic agents for COVID-19.

scholarly journals Antibiotic combinatorial approach utilized against extended spectrum beta-lactamase (ESBL) bacteria isolates from Enugu, South Eastern Nigeria

2014 ◽  
Vol 4 (1) ◽  
pp. 19-25
Author(s):  
Ruth A. Afunwa ◽  
Damian C. Odimegwu ◽  
Romanus I. Iroha ◽  
Charles O. Esimone
Keyword(s):  
Synergistic Effects ◽  
Treatment Options ◽  
Antibiotic Sensitivity ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Anal Swab ◽  
Combination Studies

Introduction: Antibiotic options in the treatment of extended spectrum beta-lactamase (ESBL) producing bacteria are very limited. The purpose of this study was to analyze several commonly applied antibiotics in quite various novel combinations for use against ESBL-producing bacteria isolates.Methods: Total of 460 samples of urine, throat and anal swab were collected from volunteers and patients from nursery, primary and secondary schools and from other individuals in the community. Hospital and community isolates comprised of 65% and 35% respectively. The identification and characterization of the isolates were done by standard culturing and in vitro antibiotic sensitivity procedures.Results: The antibiotic combination studies showed that the combination of gentamicin with the other antibiotics had predominantly synergistic effects. The percentage synergistic effect for the combinations of gentamicin/pefloxacin was 69%, gentamicin/[Amoxicillin and clavulanic acid] 72%, gentamicin/ceftriaxone 68%, gentamicin/cefuroxime 81.9%, and gentamicin/ciprofloxacin 80.6%, against the community and hospital derived ESBL producing organisms of both Enterobacteriaceae and Pseudomonas species.Conclusion: Good antimicrobial monitoring exercise and corresponding antimicrobial screening activities should work towards a dynamic approach to generate effective treatment options using combination therapy.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Clinical Management of Hypertension, Inflammation and Thrombosis in Hospitalized COVID-19 Patients: Impact on Survival and Concerns

2021 ◽  
Vol 10 (5) ◽  
pp. 1073
Author(s):  
Patricia Martínez-Botía ◽  
Ángel Bernardo ◽  
Andrea Acebes-Huerta ◽  
Alberto Caro ◽  
Blanca Leoz ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Clinical Management ◽  
Cox Regression ◽  
Angiotensin Receptor Blockers ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Hospitalized Patients ◽  
Thrombosis Prophylaxis ◽  
The Impact

The most severe clinical manifestations of the Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are due to an unbalanced immune response and a pro-thrombotic hemostatic disturbance, with arterial hypertension or diabetes as acknowledged risk factors. While waiting for a specific treatment, the clinical management of hospitalized patients is still a matter of debate, and the effectiveness of treatments to manage clinical manifestations and comorbidities has been questioned. In this study, we aim to assess the impact of the clinical management of arterial hypertension, inflammation and thrombosis on the survival of COVID-19 patients. The Spanish cohorts included in this observational retrospective study are from HM Hospitales (2035 patients) and from Hospital Universitario Central de Asturias (72 patients). Kaplan Meier survival curves, Cox regression and propensity score matching analyses were employed, considering demographic variables, comorbidities and treatment arms (when opportune) as covariates. The management of arterial hypertension with angiotensin-converting enzyme 2 (ACE2) inhibitors or angiotensin receptor blockers is not detrimental, as was initially reported, and neither was the use of non-steroidal anti-inflammatory drugs (NSAIDs). On the contrary, our analysis shows that the use on itself of corticosteroids is not beneficial. Importantly, the management of COVID-19 patients with low molecular weight heparin (LMWH) as an anticoagulant significantly improves the survival of hospitalized patients. These results delineate the current treatment options under debate, supporting the effectiveness of thrombosis prophylaxis on COVID-19 patients as a first-line treatment without the need for compromising the treatment of comorbidities, while suggesting cautiousness when administering corticosteroids.

Rash and Mucositis Associated With Mycoplasma pneumoniae and Chlamydophila pneumoniae: A Recurrence of MIRM?

2020 ◽  
Author(s):  
Danielle Brazel ◽  
Brooke Kulp ◽  
Geoanna Bautista ◽  
Andrew Bonwit
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Treatment Options ◽  
Specific Treatment ◽  
Corticosteroid Treatment ◽  
Stevens Johnson Syndrome ◽  
First Case ◽  
Johnson Syndrome ◽  
Vesicular Rash ◽  
Recurrent Aphthous Ulcers ◽  
Definition Of

Abstract Introduction A new concept has come to light recently, that is, Mycoplasma-induced rash and mucositis (MIRM). Here, we report the first case of recurrent rash, mucositis, and conjunctivitis involving Mycoplasma pneumoniae and C. pneumoniae that fits under the criteria of what is currently defined as MIRM. Case Presentation A patient aged 12 years with a history of recurrent aphthous ulcers presented in 2013 with worsening oral lesions, conjunctivitis, and vesicular rash. Her respiratory polymerase chain reaction (PCR) panel was positive for M. pneumoniae. She was diagnosed with Stevens-Johnson syndrome (SJS) secondary to M. pneumoniae and treated with a macrolide, acyclovir, and intravenous immunoglobulin (IVIG). The same patient returned 3 years later with an identical constellation of symptoms, at which time her PCR was positive for C. pneumoniae. In addition to IVIG and a macrolide, a corticosteroid treatment was administered. Discussion Here, we present the case of a pediatric patient with a recurrence of mucocutaneous disease that is more consistent with MIRM than the proposed SJS or erythema multiforme (EM) documented via histology. Our patient’s symptoms were controlled with azithromycin and IVIG and, in the second episode, with corticosteroids as well. This case adds to that of Mayor-Ibarguren et al, providing further evidence that C. pneumonia may also be a trigger for MIRM. Patients will benefit from expanding the definition of MIRM, as the pathogenesis differs from SJS and EM and could result in more specific treatment options.

scholarly journals Cellular and mitochondrial mechanisms of atrial fibrillation

2020 ◽  
Vol 115 (6) ◽  
Author(s):  
Fleur E. Mason ◽  
Julius Ryan D. Pronto ◽  
Khaled Alhussini ◽  
Christoph Maack ◽  
Niels Voigt
Keyword(s):  
Atrial Fibrillation ◽  
Nicotinamide Adenine Dinucleotide ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Specific Treatment ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Mitochondrial Activity ◽  
Atp Production

AbstractThe molecular mechanisms underlying atrial fibrillation (AF), the most common form of arrhythmia, are poorly understood and therefore target-specific treatment options remain an unmet clinical need. Excitation–contraction coupling in cardiac myocytes requires high amounts of adenosine triphosphate (ATP), which is replenished by oxidative phosphorylation in mitochondria. Calcium (Ca2+) is a key regulator of mitochondrial function by stimulating the Krebs cycle, which produces nicotinamide adenine dinucleotide for ATP production at the electron transport chain and nicotinamide adenine dinucleotide phosphate for the elimination of reactive oxygen species (ROS). While it is now well established that mitochondrial dysfunction plays an important role in the pathophysiology of heart failure, this has been less investigated in atrial myocytes in AF. Considering the high prevalence of AF, investigating the role of mitochondria in this disease may guide the path towards new therapeutic targets. In this review, we discuss the importance of mitochondrial Ca2+ handling in regulating ATP production and mitochondrial ROS emission and how alterations, particularly in these aspects of mitochondrial activity, may play a role in AF. In addition to describing research advances, we highlight areas in which further studies are required to elucidate the role of mitochondria in AF.

Management of Plantar Keratodermas

2017 ◽  
Vol 107 (5) ◽  
pp. 428-435 ◽  
Author(s):  
Rebecca M. Porter ◽  
Albert A. Bravo ◽  
Frances J.D. Smith
Keyword(s):  
Gene Therapy ◽  
Salicylic Acid ◽  
Alternative Treatment ◽  
Autosomal Dominant ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Specific Treatment ◽  
Inherited Mutations ◽  
Pachyonychia Congenita

Plantar keratodermas can arise due to a variety of genetically inherited mutations. The need to distinguish between different plantar keratoderma disorders is becoming increasingly apparent because there is evidence that they do not respond identically to treatment. Diagnosis can be aided by observation of other clinical manifestations, such as palmar keratoderma, more widespread hyperkeratosis of the epidermis, hair and nail dystrophies, or erythroderma. However, there are frequent cases of plantar keratoderma that occur in isolation. This review focuses on the rare autosomal dominant keratin disorder pachyonychia congenita, which presents with particularly painful plantar keratoderma for which there is no specific treatment. Typically, patients regularly trim/pare/file/grind their calluses and file/grind/clip their nails. Topical agents, including keratolytics (eg, salicylic acid, urea) and moisturizers, can provide limited benefit by softening the skin. For some patients, retinoids help to thin calluses but may lead to increased pain. This finding has stimulated a drive for alternative treatment options, from gene therapy to alternative nongenetic methods that focus on novel findings regarding the pathogenesis of pachyonychia congenita and the function of the underlying genes.

scholarly journals Global Spread of Mutant PfCRT and Its Pleiotropic Impact on Plasmodium falciparum Multidrug Resistance and Fitness

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Satish K. Dhingra ◽  
Stanislaw J. Gabryszewski ◽  
Jennifer L. Small-Saunders ◽  
Tomas Yeo ◽  
Philipp P. Henrich ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Treatment Options ◽  
Specific Treatment ◽  
Whole Genome Sequence ◽  
Content Type ◽  
Allelic Distribution ◽  
Population Structures ◽  
Allele Specific ◽  
Specific Parasite

Our study defines the allelic distribution of pfcrt, an important mediator of multidrug resistance in Plasmodium falciparum, in Africa and Asia. We leveraged whole-genome sequence analysis and gene editing to demonstrate how current drug combinations can select different allelic variants of this gene and shape region-specific parasite population structures. We document the ability of PfCRT mutations to modulate parasite susceptibility to current antimalarials in dissimilar, pfcrt allele-specific ways. This study underscores the importance of actively monitoring pfcrt genotypes to identify emerging patterns of multidrug resistance and help guide region-specific treatment options.

scholarly journals Congenital Deficiency in Factor VII Revealed by Menorrhagia: Case Report

2020 ◽  
pp. 1-5
Author(s):  
Nadia Mebrouk ◽  
Abdelilah Radi ◽  
Mohamed Selouti ◽  
Amal Hassani ◽  
Abdelhakim Ourrai ◽  
...  
Keyword(s):  
Treatment Options ◽  
Specific Treatment ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Activity Measurement ◽  
Recombinant Activated Factor Vii ◽  
Congenital Deficiency ◽  
Activated Factor Vii ◽  
Fresh Frozen ◽  
Fvii Deficiency

Factor VII (FVII) deficiency is the most common among rare inherited autosomal recessive bleeding disorders. It is a multifaceted disease because of the lack of a direct correlation between plasma levels of coagulation FVII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe, life-threatening bleedings (e.g., central nervous system and gastrointestinal bleeding). Menorrhagia is a frequent type of bleeding in FVII deficiency, with a prevalence rate of two in three women aged 10 to 50 years and with a peak prevalence in teenagers. When menorrhagia is observed and once the gynecological causes are excluded, it is important to carry out a hemostasis assessment because, if an anomaly is found, specific treatment can be administered and preventive measures taken. Basic diagnostic work-up includes routine assays, prothrombin level, activated partial thromboplastin time and platelet count, followed by FVII coagulant activity measurement for isolated decreased prothrombin level. To confirm the diagnosis, FVII assay should be repeated at least once. Several treatment options are currently available for FVII deficiency: Recombinant activated Factor VII (rFVIIa), plasma-derived Factor VII, fresh frozen plasma and prothrombin complex concentrates. rFVIIa is the most used replacement therapy. Other medical therapies of menorrhagia includes hemostatic agents and hormonal treatments (combined oral contraceptives, levonorgestrel intrauterine devices), in combination or not with rFVIIa. We report the case of a fourteen-and-a-half-year-old girl who presented menorrhagia of great abundance at the age of thirteen, the exploration of which revealed a congenital deficit in FVII.

scholarly journals NOS-2 Participates in the Behavioral Effects of Ethanol Withdrawal in Zebrafish

2020 ◽  
Author(s):  
Suianny Nayara da Silva Chaves ◽  
Bruna Patrícia Dutra Costa ◽  
Gabriela Cristini Vidal Gomes ◽  
Monica Lima-Maximino ◽  
Eduardo Pacheco Rico ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ethanol Withdrawal ◽  
Mechanistic Study ◽  
The Novel ◽  
Adult Zebrafish ◽  
Ethanol Abuse ◽  
Tank Test ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase ◽  
Neurobehavioral Effects

Nitric oxide has been implicated in symptoms of ethanol withdrawal in animal models. Zebrafish have been used as models to study neurobehavioral effects of ethanol (EtOH) withdrawal, but the mechanisms associated with these effects are not yet clear. Adult zebrafish were treated with 1% EtOH for 20 min per day for 8 days, injected with the nitric oxide synthase 2 (NOS-2) inhibitor aminoguanidine (50 mg/kg), and allowed to experience withdrawal (WD) in their hometanks for 7 days. EtOH WD increased anxiety-like behavior in the novel tank test, an effect that was blocked by aminoguanidine. EtOH WD also increased brain levels of nitrite, an effect that was partially blocked by aminoguanidine. These results underline a novel mechanism by which NOS-2 controls anxiety-like responses to ethanol withdrawal, with implications for the mechanistic study of symptoms associated with chronic ethanol abuse.

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

2020 ◽  
Author(s):  
Yuanyuan Wu ◽  
Weiwei Chen ◽  
Yufang Zhang ◽  
Aifen Liu ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Synergistic Effects ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Specific Treatment ◽  
Transcriptional Profile ◽  
Apoptosis And Inflammation ◽  
Active Caspase

Abstract Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation, (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-min renal bilateral ischemia and 48-h reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change > 1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6, SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

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