RESUMEN
The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.
RESUMEN
Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.
RESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.
RESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense singlestranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor – angiotensin converting enzyme 2 (ACE2) – on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene.The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.
RESUMEN
IL-32 exists as seven mRNA transcripts that can translate into distinct individual IL-32 variants with specific protein domains. These translated protein domains of IL-32 variants code for specific functions that allow for interaction with different molecules intracellularly or extracellularly. The longest variant is IL-32γ possessing 234 amino acid residues with all 11 protein domains, while the shortest variant is IL-32α possessing 131 amino acid residues with three of the protein domains. The first domain exists in 6 variants except IL-32δ variant, which has a distinct translation initiation codon due to mRNA splicing. The last eleventh domain is common domain for all seven IL-32 variants. Numerous studies in different fields, such as inflammation, autoimmunity, pathogen infection, and cancer biology, have claimed the specific biological activity of individual IL-32 variant despite the absence of sufficient data. There are 4 additional IL-32 variants without proper transcripts. In this review, the structural characteristics of seven IL-32 transcripts are described based on the specific protein domains.
Asunto(s)
Autoinmunidad , Biología , Codón Iniciador , Inflamación , Estructura Terciaria de Proteína , ARN MensajeroRESUMEN
Virus-like particles (VLPs) derived from human papillomavirus (HPV) L1 capsid proteins were used for HPV quadrivalent recombinant vaccine. The HPV quadrivalent vaccine is administrated in a 3-dose regimen of initial injection followed by subsequent doses at 2 and 6 months to prevent cervical cancer, vulvar, and vaginal cancers. The type 6, 11, 16, or 18 of HPV infection is associated with precancerous lesions and genital warts in adolescents and young women. The HPV vaccine is composed of viral L1 capsid proteins are produced in eukaryotic expression systems and purified in the form of VLPs. Four different the L1 protein of 3 different subtypes of HPV: HPV11, HPV16, and HPV18 were expressed in Escherichia coli divided into 2 fragments as N- and C-terminal of each protein in order to examine the efficacy of HPV vaccine. Vaccinated sera failed to recognize N-terminal L1 HPV type 16 and type 18 by western blot while they detected N-terminal L1 protein of HPV type 11. Moreover, the recombinant C-terminal L1 proteins of type 16 was non-specifically recognized by the secondary antibody conjugated with horseradish peroxidase. This expression and purification system may provide simple method to obtain robust recombinant L1 protein of HPV subtypes to improve biochemical analysis of antigens with immunized sera.
Asunto(s)
Adolescente , Femenino , Humanos , Western Blotting , Proteínas de la Cápside , Condiloma Acuminado , Ensayo de Inmunoadsorción Enzimática , Escherichia coli , Peroxidasa de Rábano Silvestre , Métodos , Papillomaviridae , Proteínas Recombinantes , Neoplasias del Cuello Uterino , Neoplasias VaginalesRESUMEN
The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.
Asunto(s)
Animales , Humanos , Ratones , Células de la Médula Ósea , Médula Ósea , Citocinas , Enfermedad Injerto contra Huésped , Inflamación , Interleucina-6 , Interleucinas , Membranas , Mieloblastina , Células Mieloides , Serina ProteasasRESUMEN
It has been reported that fatty acid binding proteins (FABPs) do not act only as intracellular mediators of lipid responses but also have extracellular functions. This study aimed to investigate whether extracellular liver type (L)-FABP has a biological activity and to determined serum L-FABP levels in patients with end-stage renal disease (ESRD). We isolated L-FABP complementary deoxyribonucleic acid (cDNA) from the Huh7 human hepatocarcinoma cell line and expressed the recombinant L-FABP protein in Escherichia coli. A549 lung carcinoma and THP-1 monocytic cells were stimulated with the human recombinant L-FABP. Human whole blood cells were also treated with the human recombinant L-FABP or interleukin (IL)-1α. IL-6 levels were measured in cell culture supernatants using IL-6 enzyme-linked immunosorbent assay (ELISA). Human recombinant L-FABP induced IL-6 in a dose-dependent manner in A549, THP-1 cells, and whole blood cells. The blood samples of healthy volunteers and patients with ESRD were taken after an overnight fast. The serum levels of L-FABP in healthy volunteers and ESRD patients were quantified with L-FABP ELISA. The values of L-FABP in patients with ESRD were significantly lower than those in the control group. Our results demonstrated the biological activity of L-FABP in human cells suggesting L-FABP can be a mediator of inflammation.
Asunto(s)
Humanos , Células Sanguíneas , Proteínas Portadoras , Técnicas de Cultivo de Célula , Línea Celular , ADN , Ensayo de Inmunoadsorción Enzimática , Escherichia coli , Proteínas de Unión a Ácidos Grasos , Voluntarios Sanos , Inflamación , Interleucina-6 , Interleucinas , Fallo Renal Crónico , Hígado , PulmónRESUMEN
The pro-inflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-kappaB) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.
Asunto(s)
Western Blotting , Citocinas , Interleucina-8 , Interleucinas , Fosforilación , Proteínas Quinasas , Transducción de Señal , Factor de Necrosis Tumoral alfaRESUMEN
While arthroscopic shoulder surgery is considered relatively safe, complications have been reported.Though rare, pneumothorax has been reported in patients undergoing arthroscopic shoulder surgery.Tension pneumothorax must be immediately recognized and treated due to its potentially life threatening consequences.The authors present a case of a patient who developed tension pneumothorax after arthroscopic shoulder surgery, and its anesthetic managements.
Asunto(s)
Humanos , Neumotórax , HombroRESUMEN
The aim of this study was to develop a nonlinear mixed-effects model for the increase in cerebral oximetry (rSO2) during the rapid introduction of desflurane, and to determine the effect of hypocapnia and N2O on the model. Twelve American Society of Anesthesiologist physical status class 1 and 2 subjects were allocated randomly into an Air and N2O group. After inducing anesthesia, desflurane was then increased abruptly from 4.0 to 12.0%. The PET(CO2), PET(DESF) and rSO2 were recorded at 12 predetermined periods for the following 10 min. The maximum increase in rSO2 reached +24-25% during normocapnia. The increase in rSO2 could be fitted to a four parameter logistic equation as a function of the logarithm of PET(DESF). Hypocapnia reduced the maximum response of rSO2, shifted the EC50 to the right, and increased the slope in the Air group. N2O shifted the EC50 to the right, and reduced the slope leaving the maximum rSO2 unchanged. The N2O-effects disappeared during hypocapnia. The cerebrovascular reactivity of rSO2 to CO2 is still preserved during the rapid introduction of desflurane. N2O slows the response of rSO2. Hypocapnia overwhelms all the effects of N2O.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anestésicos por Inhalación/farmacología , Corteza Cerebral/irrigación sanguínea , Circulación Cerebrovascular/efectos de los fármacos , Hemodinámica , Hipocapnia/metabolismo , Isoflurano/análogos & derivados , Modelos Teóricos , Óxido Nitroso/metabolismo , Oximetría , Distribución Aleatoria , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
An epiglottic cyst is a common form of laryngeal cysts which are rare causes of upper airway obstruction. A congenital laryngeal cyst always causes neonatal respiratory distress, but an acquired cyst shows very wide spectrum of symptoms such as no specific complaints, dysphagia, respiratory difficulty, or even death according to its size, location, or age. From anesthesiologists' point of view, an asymptomatic undiagnosed laryngeal cyst is a major concern. Unexpectedly, it can cause difficult airway such as 'cannnot intubate' or 'cannot intubate and cannot ventilate' situation during anesthesia. Recently we discovered an undiagnosed epiglottic cyst obscuring laryngeal inlet, leading to difficult intubation during general anesthesia for decompression and fusion of lumbar vertebrae. Fortunately, mask ventilation was possible, and after failed attempts of direct laryngoscopy, we could perform oral fiberoptic bronchoscope-aided intubation. He was discharged 10 days later with no harmful events.