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1.
Curr Issues Mol Biol ; 45(1): 400-433, 2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36661514

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome) is highly infectious and causes severe acute respiratory distress syndrome (SARD), immune suppression, and multi-organ failure. For SARS-CoV-2, only supportive treatment options are available, such as oxygen supportive therapy, ventilator support, antibiotics for secondary infections, mineral and fluid treatment, and a significant subset of repurposed effective drugs. Viral targeted inhibitors are the most suitable molecules, such as ACE2 (angiotensin-converting enzyme-2) and RBD (receptor-binding domain) protein-based inhibitors, inhibitors of host proteases, inhibitors of viral proteases 3CLpro (3C-like proteinase) and PLpro (papain-like protease), inhibitors of replicative enzymes, inhibitors of viral attachment of SARS-CoV-2 to the ACE2 receptor and TMPRSS2 (transmembrane serine proteinase 2), inhibitors of HR1 (Heptad Repeat 1)-HR2 (Heptad Repeat 2) interaction at the S2 protein of the coronavirus, etc. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein's ability to fuse to the membrane. Even with the tremendous progress made, creating effective drugs remains difficult. To develop COVID-19 treatment alternatives, clinical studies are examining a variety of therapy categories, including antibodies, antivirals, cell-based therapy, repurposed diagnostic medicines, and more. In this article, we discuss recent clinical updates on SARS-CoV-2 infection, clinical characteristics, diagnosis, immunopathology, the new emergence of variant, SARS-CoV-2, various approaches to drug development and treatment options. The development of therapies has been complicated by the global occurrence of many SARS-CoV-2 mutations. Discussion of this manuscript will provide new insight into drug pathophysiology and drug development.

2.
Cells ; 11(23)2022 Nov 25.
Article in English | MEDLINE | ID: mdl-36497027

ABSTRACT

Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction. If insulin has neuroprotective properties, insulin resistance may interfere with those properties. Risk factors have a significant impact on the development of diseases, such as diabetes, obesity, stroke, and other conditions. Analysis of risk factors of importance for the association between diabetes and dementia is important because they may impede clinical management and early diagnosis. We discuss the pathological and physiological mechanisms behind the association between Type 2 diabetes mellitus and dementia, such as insulin resistance, insulin signaling, and sporadic forms of dementia; the relationship between insulin receptor activation and TAU phosphorylation; dementia and mRNA expression and downregulation of related receptors; neural modulation due to insulin secretion and glucose homeostasis; and neuronal apoptosis due to insulin resistance and Type 2 diabetes mellitus. Addressing these factors will offer clinical outcome-based insights into the mechanisms and connection between patients with type 2 diabetes and cognitive impairment. Furthermore, we will explore the role of brain insulin resistance and evidence for anti-diabetic drugs in the prevention of dementia risk in type 2 diabetes.


Subject(s)
Dementia , Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Insulin Resistance/physiology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Insulin/metabolism , Dementia/complications , Dementia/drug therapy
3.
Int J Mol Sci ; 23(12)2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35743111

ABSTRACT

For the industrial-scale production of useful enzymes by microorganisms, technological development is required for overcoming a technical bottleneck represented by poor efficiency in the induction of enzyme gene expression and secretion. In this study, we evaluated the potential of a non-thermal atmospheric pressure plasma jet to improve the production efficiency of cellulolytic enzymes in Neurospora crassa, a filamentous fungus. The total activity of cellulolytic enzymes and protein concentration were significantly increased (1.1~1.2 times) in media containing Avicel 24-72 h after 2 and 5 min of plasma treatment. The mRNA levels of four cellulolytic enzymes in fungal hyphae grown in media with Avicel were significantly increased (1.3~17 times) 2-4 h after a 5 min of plasma treatment. The levels of intracellular NO and Ca2+ were increased in plasma-treated fungal hyphae grown in Avicel media after 48 h, and the removal of intracellular NO decreased the activity of cellulolytic enzymes in media and the level of vesicles in fungal hyphae. Our data suggest that plasma treatment can promote the transcription and secretion of cellulolytic enzymes into the culture media in the presence of Avicel (induction condition) by enhancing the intracellular level of NO and Ca2+.


Subject(s)
Cellulase , Neurospora crassa , Cellulase/metabolism , Cellulose/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Neurospora crassa/genetics
4.
Int J Mol Sci ; 23(12)2022 Jun 12.
Article in English | MEDLINE | ID: mdl-35743012

ABSTRACT

Oocyte in vitro maturation (IVM) is the most important first step in in vitro embryo production. One prerequisite for the success of IVM in oocytes is to provide a rich culture microenvironment that meets the nutritional needs of developing oocytes. We applied different equine amniotic fluid mesenchymal stem cell conditioned medium (eAFMSC-CM) from passages 7, 18, and 27 to porcine oocytes during IVM to determine its effects on oocyte development and subsequent embryo development, specifically. The eAFMSC-CM from passage 7 (eAFMSC-CMp7) has a considerable impact on 9 genes: BAX, BCL2, SOD2, NRF2, TNFAIP6, PTGS2, HAS2, Cx37, and Cx43, which are associated with cumulus cell mediated oocyte maturation. GSH levels and distribution of mitochondrial and cortical granules were significantly increased in oocytes incubated with eAFMSC-CMp7. In addition, catalase and superoxide dismutase activities were high after IVM 44 h with eAFMSC-CMp7. After in vitro fertilization, blastocyst quality was significantly increased in the eAFMSC-CMp7 group compared to control. Lastly, the antioxidant effect of eAFMSC-CMp7 substantially regulated the expression of apoptosis, pluripotency related genes and decreased autophagy activity in blastocysts. Taken together, this study demonstrated that the eAFMSC-CMp7 enhanced the cytoplasmic maturation of oocytes and subsequent embryonic development by generating high antioxidant activity.


Subject(s)
Amniotic Fluid , Mesenchymal Stem Cells , Animals , Blastocyst/metabolism , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Cumulus Cells/metabolism , Embryonic Development/genetics , Female , Fertilization in Vitro , Horses , In Vitro Oocyte Maturation Techniques/veterinary , Oocytes/metabolism , Pregnancy , Swine
5.
Int J Mol Sci ; 24(1)2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36613714

ABSTRACT

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin family that is overexpressed in several cancers. RAGE is highly expressed in the lung, and its expression increases proportionally at the site of inflammation. This receptor can bind a variety of ligands, including advanced glycation end products, high mobility group box 1, S100 proteins, adhesion molecules, complement components, advanced lipoxidation end products, lipopolysaccharides, and other molecules that mediate cellular responses related to acute and chronic inflammation. RAGE serves as an important node for the initiation and stimulation of cell stress and growth signaling mechanisms that promote carcinogenesis, tumor propagation, and metastatic potential. In this review, we discuss different aspects of RAGE and its prominent ligands implicated in cancer pathogenesis and describe current findings that provide insights into the significant role played by RAGE in cancer. Cancer development can be hindered by inhibiting the interaction of RAGE with its ligands, and this could provide an effective strategy for cancer treatment.


Subject(s)
Neoplasms , Receptor for Advanced Glycation End Products , Humans , Glycation End Products, Advanced/metabolism , Inflammation/metabolism , Ligands , Neoplasms/drug therapy , Receptor for Advanced Glycation End Products/antagonists & inhibitors
6.
Front Chem ; 10: 1064191, 2022.
Article in English | MEDLINE | ID: mdl-36712982

ABSTRACT

Recent times have seen a strong surge in therapeutically targeting the hedgehog (HH)/GLI signaling pathway in cervical cancer. HH signaling pathway is reported to be a crucial modulator of carcinogenesis in cervical cancer and is also associated with recurrence and development of chemoresistance. Moreover, our previous reports have established that carvacrol (CAR) inhibited the proliferation of prostate cancer cells via inhibiting the Notch signaling pathway and thus, it was rational to explore its antiproliferative effects in cervical cancer cell lines. Herein, the present study aimed to investigate the anticancer and apoptotic potential of CAR on C33A cervical cancer cells and further explore the underlying mechanisms. We found that CAR significantly suppressed the growth of C33A cells, induced cell cycle arrest, and enhanced programmed cell death along with augmentation in the level of ROS, dissipated mitochondrial membrane potential, activation of caspase cascade, and eventually inhibited the HH signaling cascade. In addition, CAR treatment increased the expression of pro-apoptotic proteins (Bax, Bad, Fas-L, TRAIL, FADDR, cytochrome c) and concomitantly reduced the expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) in C33A cells. CAR mediates the activation of caspase-9 and -3 (intrinsic pathway) and caspase-8 (extrinsic pathway) accompanied by the cleavage of PARP in cervical cancer cells. Thus, CAR induced apoptosis by both the intrinsic and extrinsic apoptotic pathways. CAR efficiently inhibited the growth of cervical cancer cells via arresting the cell cycle at G0/G1 phase and modulated the gene expression of related proteins (p21, p27, cyclin D1 and CDK4). Moreover, CAR inhibited the HH/GLI signaling pathway by down regulating the expression of SMO, PTCH and GLI1 proteins in cervical carcinoma cells. With evidence of the above results, our data revealed that CAR treatment suppressed the growth of HPV-C33A cervical cancer cells and further elucidated the mechanistic insights into the functioning of CAR.

7.
Biomedicines ; 9(11)2021 Nov 04.
Article in English | MEDLINE | ID: mdl-34829850

ABSTRACT

The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been proposed. These medicines include inhibitors of serine protease TMPRSS2 and angiotensin converting enzyme 2 (ACE2). The S protein of SARS-CoV-2 binds to the receptor in host cells. ACE2 inhibitors block TMPRSS2 and S protein priming, thus preventing SARS-CoV-2 entry to host cells. Moreover, antiviral medicines (including the nucleotide analogue remdesivir, the HIV protease inhibitors lopinavir and ritonavir, and wide-spectrum antiviral antibiotics arbidol and favipiravir) have been shown to reduce the dissemination of SARS-CoV-2 as well as morbidity and mortality associated with COVID-19.

8.
Foods ; 10(8)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34441665

ABSTRACT

Although non-thermal atmospheric pressure plasma is an efficient tool for preventing post-harvest microbial contamination, many studies have focused on the post-treatment of infected or contaminated foods. In this study, we examined the antimicrobial quality of mushrooms pre-treated with a non-thermal atmospheric pressure plasma jet (NTAPPJ) or plasma-treated water (PTW). The CFU (Colony Forming Unit) number of Escherichia coli inoculated on surfaces of mushrooms pre-treated with NTAPPJ or PTW was significantly reduced (about 60-75% for NTAPPJ and about 35-85% for PTW), and the reduction rate was proportional to the treatment time. Bacterial attachment and viability of the attached bacteria were decreased on NTAPPJ-treated mushroom surfaces. This may be caused by the increased hydrophilicity and oxidizing capacity observed on NTAPPJ-treated mushroom surfaces. In PTW-treated mushrooms, bacterial attachment was not significantly changed, but death and lipid peroxidation of the attached bacteria were significantly increased. Analysis of mushroom quality showed that loss of water content was greater in mushrooms treated with NTAPPJ compared to that in those with no treatment (control) and PTW treatment during storage. Our results suggest that pre-treatment with NTAPPJ or PTW can improve the antibacterial quality of mushroom surfaces by decreasing bacterial attachment (for NTAPPJ) and increasing bacterial lipid peroxidation (for both NTAPPJ and PTW).

9.
Comput Struct Biotechnol J ; 19: 2384-2397, 2021.
Article in English | MEDLINE | ID: mdl-34025931

ABSTRACT

Breast cancer (BC) is the most common type of cancer in women at the global level and the highest mortality rate has been observed with triple-negative breast cancer (TNBC). Accumulation of genetic lesions an aberrant gene expression and protein degradation are considered to underlie the onset of tumorigenesis and metastasis. Therefore, the challenge to identify the genes and molecules that could be potentially used as potent biomarkers for personalized medicine against TNBC with minimal or no associated side effects. Discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) arrangement and an increasing repertoire of its new variants has provided a much-needed fillip towards editing TNBC genomes. In this review, we discuss the CRISPR/Cas9 genome editing, CRISPR Technology for diagnosis of (Triple-negative breast cancer) TNBC, Drug Resistance, and potential applications of CRISPR/Cas9 and its variants in deciphering or engineering intricate molecular and epigenetic mechanisms associated with TNBC. Furthermore, we have also explored the TNBC and CRISPR/Cas9 genome editing potential for repairing, genetic modifications in TNBC.

10.
J Periodontal Implant Sci ; 51(1): 53-62, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33634615

ABSTRACT

PURPOSE: This study aimed to evaluate the clinical and microbiological efficacy of adjunctive local delivery of minocycline (Periocline®) in patients receiving supportive periodontal therapy (SPT) after initial treatment. METHODS: The participants were 16 men and 8 women (age, 20-65 years) who had at least 15 natural teeth, underwent SPT for more than 1 year due to chronic periodontitis, had 4 or more periodontal pocket sites deeper than 5 mm, and showed >25% gingival bleeding on probing (BoP). They were randomly assigned to the test and control groups. In the test group, mechanical debridement and local antibiotic delivery were performed for all periodontal sulci/pockets; in the control group, mechanical debridement and saline irrigation were performed. In patients who underwent SPT for more than 1 year, clinical and microbiological examinations were performed at baseline and 1 and 3 months after SPT. The clinical examination included an assessment of the periodontal pocket depth, clinical attachment level, plaque index, and BoP. Microbial tests were performed using real-time polymerase chain reaction; the relative ratios of Porphyromonas gingivalis and Fusobacterium nucleatum were determined. RESULTS: Both groups showed significant improvements in clinical parameters at 1 and 3 months from baseline; there were no significant changes between months 1 and 3. Intergroup differences were insignificant. The microbiological analysis revealed no significant differences in P. gingivalis and F. nucleatum ratios across time points. While intergroup differences were insignificant, there was a tendency for the P. gingivalis and F. nucleatum ratios to decrease in the test group. CONCLUSIONS: Mechanical debridement in patients receiving maintenance therapy resulted in clinically significant improvement; the effectiveness of additional local delivery of antibiotics was not significant. The ratios of P. gingivalis and F. nucleatum showed a tendency to decrease in the test group, although it was not significant.

11.
Nanomaterials (Basel) ; 12(1)2021 Dec 30.
Article in English | MEDLINE | ID: mdl-35010068

ABSTRACT

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide-zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO-CS), a zinc oxide decorated graphene oxide-chitosan nanocomposite (GO-CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

12.
J Biomol Struct Dyn ; 39(4): 1343-1353, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32072876

ABSTRACT

Electroporation processes affect the permeability of cell membranes, which can be utilized for the delivery of plasma species in cancer therapy. By means of computational dynamics, many aspects of membrane electroporation have been unveiled at the atomic level for lipid membranes. Herein, a molecular dynamics simulation study was performed on native and oxidized membrane systems with transversal electric fields. The simulation result shows that the applied electric field mainly affects the membrane properties so that electroporation takes place and these pores are lined by hydrophilic headgroups of the lipid components. The calculated hydrophobic thickness, lateral diffusion and pair correlation revealed the role of 5α-CH in creation of water-pore in an oxidized membrane. Additionally, the permeability of reactive oxygen species was examined through these electroporated systems. The permeability study suggested that water pores in the membrane facilitate the penetration of these species across the membrane to the interior of the cell. These findings may have significance in experimental applications in vivo as once the reactive oxygen species reaches the interior of the cell, they may cause oxidative stress and induce apoptosis.Communicated by Ramaswamy H. Sarma.


Subject(s)
Electroporation , Lipid Bilayers , Cell Membrane , Molecular Dynamics Simulation , Reactive Oxygen Species
13.
Microb Biotechnol ; 14(1): 262-276, 2021 01.
Article in English | MEDLINE | ID: mdl-33151631

ABSTRACT

Technical bottlenecks in protein production and secretion often limit the efficient and robust industrial use of microbial enzymes. The potential of non-thermal atmospheric pressure plasma to overcome these technical barriers was examined. Spores of the fermenting fungus Aspergillus oryzae (A. oryzae) were submerged in potato dextrose broth (PDB) (5 × 106 per ml) and treated with micro dielectric barrier discharge plasma at an input voltage of 1.2 kV and current of 50 to 63 mA using nitrogen as the feed gas. The specific activity of α-amylase in the broth was increased by 7.4 to 9.3% after 24 and 48 h of plasma treatment. Long-lived species, such as NO2 - and NO3 - , generated in PDB after plasma treatment may have contributed to the elevated secretion of α-amylase. Observations after 24 h of plasma treatment also included increased accumulation of vesicles at the hyphal tip, hyphal membrane depolarization and higher intracellular Ca2+ levels. These results suggest that long-lived nitrogen species generated in PDB after plasma treatment can enhance the secretion of α-amylase from fungal hyphae by depolarizing the cell membrane and activating Ca2+ influx into hyphal cells, eventually leading to the accumulation of secretory vesicles near the hyphal tips.


Subject(s)
Aspergillus oryzae , Plasma Gases , alpha-Amylases/biosynthesis , Aspergillus oryzae/enzymology , Cell Membrane , Hyphae , Industrial Microbiology , Nitrogen
14.
Front Cell Dev Biol ; 8: 580202, 2020.
Article in English | MEDLINE | ID: mdl-33240881

ABSTRACT

The coronavirus (SARS-CoV-2) pandemic is a rapidly transmitting and highly pathogenic disease. The spike protein of SARS-CoV-2 binds to the surface of angiotensin-converting enzyme-2 (ACE2) receptors along the upper respiratory tract and intestinal epithelial cells. SARS-CoV-2 patients develop acute respiratory distress, lymphocytic myocarditis, disseminated intravascular coagulation, lymphocytic infiltration, and other serious complications. A SARS-CoV-2 diagnosis is conducted using quantitative reverse-transcription PCR and computed tomography (CT) imaging. In addition, IgM or IgG antibodies are used to identify acute and convalescent illness. Recent clinical data have been generated by health workers and researchers and have shown that there is an urgent requirement in the effective clinical and treatment of patients, as well as other developments for dealing with SARS-CoV-2 infection. A broad spectrum of clinical trials of different vaccines and drug treatment has been evaluated for use against SARS-CoV-2. This review includes the emergence of SARS-CoV-2 pneumonia as a way to recognize and eliminate any barriers that affect rapid patient care and public health management against the SARS-CoV-2 epidemic based on the natural history of the disease, its transmission, pathogenesis, immune response, epidemiology, diagnosis, clinical presentation, possible treatment, drug and vaccine development, prevention, and future perspective.

15.
Comput Struct Biotechnol J ; 18: 3774-3787, 2020.
Article in English | MEDLINE | ID: mdl-33235690

ABSTRACT

Coronaviruses are a group of enveloped RNA viruses that are diversely found in humans and now declared a global pandemic by the World Health Organization in March 2020. The population's susceptibility to these highly pathogenic coronaviruses has contributed to large outbreaks, evolved into public health events, and rapidly transmitted globally. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In the primary stage of severe acute respiratory syndrome coronavirus (SARS-COV-2) infection, the signs and symptoms are nonspecific, and many more cases have been observed than initially expected. Genome sequencing is performed regularly to identify genetic changes to SARS-COV-2, and vaccine development is focused on manufacture, production, and based on specific problems, and very few are available on recent developments in the prevention of outbreaks. The aim of this review article to explore recent updates on SARS-COV-2 in the context of pathogenesis during disease progression, and innate acquired mechanisms of defense, This includes advances in diagnostics, susceptibility, and severity of host-virus genome interactions, modes of transmission, active compounds being used in pre-clinical and clinical trials for the treatment of patients, vaccine developments, and the effectiveness of SARS-COV-2 prevention and control measures. We have summarized the importance of pathophysiology immune response, Diagnostics, vaccine development currently approaches explored for SARS-COV-2.

16.
Int J Med Sci ; 17(12): 1811-1818, 2020.
Article in English | MEDLINE | ID: mdl-32714084

ABSTRACT

Herpes zoster develops when latent varicella zoster virus is reactivated in the trigeminal or dorsal root ganglions. Zoster-associated pain (ZAP) is neuropathic pain caused by the herpes zoster virus. Histological studies of postherpetic neuralgia patients suggest that inflammation is involved in ZAP. The effectiveness of local anesthetic and steroid epidural injections in ZAP patients has been reported. However, most studies included patients with acute herpes zoster, and the safety and therapeutic effects of different doses of epidural steroids in ZAP patients remain elusive. In this study, we randomly assigned 42 patients with severe ZAP beyond the acute phase, as determined by a numeric rating scale (NRS) score ≥7, to receive continuous epidural infusion of local anesthetics with either a one-time 5-mg dose or intermittent repeated doses (15 mg total) of dexamethasone. We found that intermittent repeated epidural dexamethasone bolus resulted in reduced NRS scores and an increased likelihood of complete remission in ZAP patients without any adverse effects. Thus, our results suggest that intermittent repeated epidural dexamethasone administration is safe and effective for treatment of ZAP beyond the acute phase.


Subject(s)
Dexamethasone/administration & dosage , Herpes Zoster/drug therapy , Neuralgia, Postherpetic/drug therapy , Neuralgia/drug therapy , Aged , Analgesia, Epidural/methods , Anesthesia, Epidural/methods , Anesthetics, Local/administration & dosage , Anesthetics, Local/adverse effects , Dexamethasone/adverse effects , Female , Ganglia, Spinal/drug effects , Ganglia, Spinal/pathology , Herpes Zoster/complications , Herpes Zoster/pathology , Humans , Injections, Epidural , Male , Middle Aged , Neuralgia/complications , Neuralgia/pathology , Neuralgia, Postherpetic/pathology , Pain Measurement/methods
17.
Bioorg Med Chem Lett ; 30(14): 127242, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32527544

ABSTRACT

Epipyrone (EPN)-A (syn. orevactaene) is a polyketide compound of 3-d-galactosyl-4-hydroxy-2-pyrone with a modified heptaene acyl moiety, produced from Epicoccum nigrum and was reported to have various biological activities. Genome analysis identified a hypothetical EPN biosynthetic gene cluster (BGC) composed of the four genes epnABCD, which encode a highly-reducing fungal polyketide synthase, a glycosyltransferase, a cytochrome P450, and a transporter. The individual gene inactivation of epnABC resulted in the total loss of EPN production, while the inactivation of a nearby transcription factor-encoding gene had no effect on the production of EPN, substantiating that epnABCD is the EPN BGC. mRNA expression indicated no epnA transcription in the epnB knockout mutant and the occurrence of the bicistronic transcription of epnAB. This study defined an EPN BGC, which is the first blueprint reported for glycosylated 2-pyrone polyketide biosynthesis.


Subject(s)
Ascomycota/chemistry , Ascomycota/genetics , Pyrans/metabolism , Molecular Conformation , Multigene Family , Pyrans/chemistry
18.
Front Chem ; 8: 250, 2020.
Article in English | MEDLINE | ID: mdl-32351935

ABSTRACT

Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

19.
Sci Rep ; 10(1): 3396, 2020 02 25.
Article in English | MEDLINE | ID: mdl-32099012

ABSTRACT

Malignant melanoma is considered to be a heterogeneous disease that arises from altered genes and transformed melanocytes. In this study, special softjet cold atmospheric plasma was used to treat three different human melanoma cells using air and N2 gases to check the anti-melanoma activity. The physical effects by plasma revealed an increase in the temperature with the gradual reduction in pH at 60 sec, 180 sec and 300 sec air and N2 plasma treatment. Cellular toxicity revealed a decreased in cell survival (~50% cell survival using air gas and <~60% cell survival using N2 gas at 60 sec plasma treatment in G-361 cells). Gene analysis by q-PCR revealed that 3 min and 5 min air and N2 plasma treatment activated apoptotic pathways by triggering apoptotic genes in all three melanoma cell lines. The apoptosis was confirmed by DAPI staining and its related pathways were further explored according to protein-protein docking, and their probable activation mechanism was revealed. The pathways highlighted that activation of apoptosis which leads to cellular cascades and hence stimulation ASK1 (docking method) revealed that softjet plasma can be an effective modality for human melanoma treatment.


Subject(s)
Apoptosis , Computer Simulation , Melanoma/metabolism , Plasma Gases , Cell Line, Tumor , Free Radicals/chemistry , Free Radicals/pharmacology , Humans , Plasma Gases/chemistry , Plasma Gases/pharmacology
20.
Zootaxa ; 4896(2): zootaxa.4896.2.2, 2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33756862

ABSTRACT

Two new planktonic ostracods of the genus Proceroecia Kock, 1992, P. hwanghaensis sp. nov. and P. joseondonghaensis sp. nov., collected from neritic waters off the south coast of South Korea are described. Morphologically, they are similar to P. microprocera (Angel, 1971), the type species of the genus, but show several clear morphological differences, most prominent being the shape of the male endopodite on the second antenna and the presence of a sensilla on the coxale of the fifth limb. The two new species have subtle differences, such as the length of the frontal organ, number of spines on the comb-like e-seta on the first antenna in males, number of spinules on the b-seta on the second antenna in females, etc. Sequences derived from partial mitochondrial cytochrome oxidase c subunit 1 (mtCOI) for these novel species have been compared with sequences available for other Proceroecia species on GenBank, including P. microprocera. These comparisons suggest that both new species are distinct taxa. They also indicate that one set of sequences on GeneBank previously attributed to P. microprocera and derived from material collected from Chinese waters, belong to P. hwanghaensis, and that another set of sequences of an unidentified Proceroecia species from the South China Sea can be attributable to P. joseondonghaensis. Hence, these new species occur widely in the neritic waters of East Asia. The present study increases the number of the known Proceroecia species to nine, and the numbers of halocyprid ostracod species recorded from Korean waters to six.


Subject(s)
Crustacea , Plankton , Animals , Crustacea/genetics , Female , Male , Republic of Korea
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