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Abstract Osteoporosis is manifested by decreased bone density and deterioration of bone architecture, increasing the risk of bone fractures Human bone marrow mesenchymal stem cells (hBMSCs)-based tissue engineering serves as a crucial technique for regenerating lost bone and preventing osteoporosis. Non-thermal biocompatible plasma (NBP) is a potential new therapeutic approach employed in several biomedical applications, including regenerative medicine. NBP affects bone remodeling; however, its role in the regulation of osteogenic differentiation in hBMSCs remains largely unexplored. This study aimed to explore the efficiency of NBP in promoting osteogenic differentiation, and the molecular pathways through which these responses occurred in hBMSCs. We found that NBP facilitated osteogenic differentiation through the upregulation of the bone morphogenic protein signal (BMPs) cascade, which in turn induced the expression of p38 and inhibited the forkhead box protein O1 (FOXO1). To further gain insight into the mechanism through which NBP extensively triggers the initiation of osteogenic differentiation in hBMSCs, PI3K/AKT pathway was also analyzed. Overall, these results highlight that NBP enhances osteogenic differentiation in hBMSCs by the stimulation of the p38/FOXO1 through PI3K/AKT signaling pathways. Therefore, the application of NBP in hBMSCs may offer tremendous therapeutic prospects in the treatment of bone regeneration and osteoporosis prevention.

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.

Global society has been highly pressured by the COVID-19 pandemic, which has exposed vulnerabilities in supply chains for disinfection products, personal protective equipment, and medical resources worldwide. It is critically necessary to find effective treatments and medications for these viral infections. This review summarizes and emphasizes critical features of recent breakthroughs in vaccines, inhibitors, radiations, and innovative nonthermal atmospheric plasma (NTAP) technologies to inactivate COVID-19. NTAP has emerged as an effective, efficient, and safe method of viral inactivation. NTAP can be used to inactivate viruses in an environmentally friendly manner, as well as activate animal and plant viruses in a variety of matrices. Researchers and engineers desire to help the medical world deal with the ongoing COVID-19 epidemic by establishing techniques that make use of widely available NTAP technologies. NTAP technology is not dependent on viral strain, and it does not necessitate months or years of research to develop specific vaccines for each novel or arising viral disease. We believe the NTAP is a highly promising technique for combating COVID-19 and other viruses. Thus, NTAP technology could be a significant breakthrough in the near future in assisting humans in combating COVID-19 infections. We hope that this review provides a platform for readers to examine the progress made in the fight against COVID-19 through the use of vaccines, inhibitors, radiation, and NTAP.

Background: Pulsed high-power microwave (HPM) has many applications and is constantly being researched to expand its uses in the future. As the number of applications grows, the biological effects and safety level of pulsed HPM become a serious issue, requiring further research.Objective: The brain is regarded as the most vulnerable organ to radiation, raising concerns about determining an acceptable level of exposure. The effect of nanosecond pulses and the mechanisms underlying HPM on the brain has not been studied. For the first time, we observed the effect of pulsed 3.5 GHz HPM on brain normal astrocytes and cancer U87 MG cells, as well as the likely mechanisms involved.Methods: To generate 3.5 GHz HPM, an axial virtual cathode oscillator was constructed on pulsed power generator “Chundoong”. The cells were directly exposed to HPM (10, 25, 40, and 60) pulses (1 mJ/pulse), with each pulse delivered after 1 min of charging time to evaluate the dose dependent effects.Results: A strong electric field (∼23 kV/cm) of HPM irradiation primarily causes the production of reactive oxygen species (ROS), altering cell viability, mitochondrial activity, and cell death rates in U87 and astrocytes at certain dosages. The ROS generation in response to HPM exposure was primarily responsible for DNA damage and p53 activation. The hazardous dosage of 60 pulses is acknowledged as having damaging effects on brain normal cells. Interestingly, the particular 25 pulses exhibited therapeutic effects on U87 cells via p53, Bax, and Caspase-3 activation.Conclusion: HPM pulses induced apoptosis-related events such as ROS burst and increased oxidative DNA damage at higher dosages in normal cells and specific 25 pulses in cancer U87. These findings are useful to understand the physiological mechanisms driving HPM-induced cell death, as well as the safety threshold range for HPM exposure on normal cells and therapeutic effects on cancer U87. As HPM technology advances, we believe this study is timely and will benefit humanity and future research.

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.

Vaginal cancer is a rare and uncommon disease that is rarely discussed. Although vaginal cancer traditionally occurs in older postmenopausal women, the incidence of high-risk human papillomavirus (HPV)-induced cancers is increasing in younger women. Cervical cancer cells contain high-risk human papillomavirus (HPV) E6 and E7 proteins and inhibiting HPV gene expression leads the cells to stop proliferating and enter senescence. As E6, and E7 protein promoted the carcinogenesis mechanism, and here not only regulate the cellular degradation of P53, and pRb but also enhances the cell proliferation along with E6 protein targets the p53 for breakdown and subsequently promote the apoptotic cell death, and DNA repair inhibition, that is indispensable to the continue the lifecycle of the HPV. As a synchronous or metachronous tumor, vaginal cancer is frequently found in combination with cervical cancer. It is uncertain what causes invasive female vaginal organ cancer. HPV type 16 is the most often isolated HPV type in female vaginal organ cancers. Due to cancer’s rarity, case studies have provided the majority of etiologic findings. Many findings demonstrate that ring pessaries, chronic vaginitis, sexual behavior, birth trauma, obesity, vaginal chemical exposure, and viruses are all risk factors. Because of insufficient understanding and disease findings, we are trying to find the disease’s mechanism with the available data. We also address different risk factors, therapy at various stages, diagnosis, and management of vaginal cancer in this review.

Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.

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.

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.

The application of non-thermal bio-compatible plasma (NBP) for stem cell differentiation is promising in tissue engineering. However, the differentiation efficiency of NBP treatment on various types of human tissue-derived stem cells and the underlying mechanisms is yet understood. This study is the first time to investigate the role of NBP in inducing differentiation and its potential molecular mechanism by using human bone marrow-derived stem cells (hBMSCs) and human periodontal ligament-derived stem cells (hPDLSCs). Our results showed that NBP promote osteogenic differentiation of hPDLSCs more effectively than hBMSCs under the same treatment condition, indicating a tissue-dependent manner of NBP interacts with stem cells. Furthermore, an increase of intracellular reactive oxygen species (ROS) production of hPDLSCs and antioxidant enzymes activation was observed after NBP treatment. Particularly, mitogen-activated protein kinases (MAPKs) level was also increased and in consistent with ROS level increase. Taken together, this study revealed that with NBP induction, hPDLSCs is a more suitable stem cell source than hBMSCs for bone regeneration and tissue engineering, and ROS-induced activation of MAPKs are possibly involved in the osteogenic differentiation process.

Calcium magnesium carbonate nanoparticles (CaMg(CO3)2 NPs), well-known as dolomite, are formed by the replacement of half of the calcite minerals of limestone. The dolomite (CaMg(CO3)2) nanoparticles are composed of calcite (CaCO3) and magnesium carbonate (MgCO3), both of which offer promising strategies for maintaining growth and development in mammals and agricultural plants. A grounded mixture of dolomite limestone was prepared via colloidal precipitates for the synthesis of CaMg(CO3)2 NPs, and their characteristics were examined using XRD, particle size analysis by DLS, and surface morphology by SEM and TEM. X-ray photoelectron spectroscopy was used to investigate the binding energy of each element of the dolomite NPs. Spectroscopy revealed that colloidal precipitation is the ideal method for producing NPs. We assessed the numerous beneficial impacts of CaMg(CO3)2 NPs in diverse sectors such as agriculture, cancer treatment, and microbiology in this study. Furthermore, an in vivo study was also carried out on chickens to observe the effects of CaMg(CO3)2 NPs. The obtained results showed that the treated group with CaMg(CO3)2 NPs maintained a more uniform calcium absorption rate than the control group did. The findings of this study suggest that CaMg(CO3)2 NPs operate as a stimulant for plants and as an inhibitory agent for bacteria and cancer cells.

The coronavirus disease (COVID-19) pandemic has placed a massive impact on global civilization. Finding effective treatments and drugs for these viral diseases was crucial. This paper outlined and highlighted key elements of recent advances in nonthermal biocompatible plasma (NBP) technology for antiviral applications. We searched for papers on NBP virus inactivation in PubMed ePubs, Scopus, and Web of Science databases. The data and relevant information were gathered in order to establish a mechanism for NBP-based viral inactivation. NBP has been developed as a new, effective, and safe strategy for viral inactivation. NBP may be used to inactivate viruses in an ecologically friendly way as well as activate animal and plant viruses in a number of matrices. The reactive species have been shown to be the cause of viral inactivation. NBP-based disinfection techniques provide an interesting solution to many of the problems since they are simply deployable and do not require the resource-constrained consumables and reagents required for traditional decontamination treatments. Scientists are developing NBP technology solutions to assist the medical community in dealing with the present COVID-19 outbreak. NBP is predicted to be the most promising strategy for battling COVID-19 and other viruses in the future.

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.

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.

Plant-derived substances exhibit antioxidant and antibacterial activities and have been proven to have beneficial effects in wound healing and skin regeneration. Plant stem cells have recently received much attention as research materials in cosmetic development because they promote regeneration after damage. In this paper, we demonstrate for the first time that the plasma treatment of stem cells obtained from rice-seed embryos can be effective in enhancing antioxidant activity and in regenerating human skin. We investigated this potential utilizing micro-DBD (Dielectric Barrier Discharge) plasma as a pretreatment technique to enhance the vitality and functional activity of rice stem cells. The results of the cell culture experiments show that plasma-treated rice stem cell extracts (RSCE) have promising antioxidant and anti-skin aging activities. The results of quantitative real-time PCR (qRT-PCR) for major antioxidant enzymes and anti-aging genes confirm that the plasma technique used in the pretreatment of RSCE was able to enhance cell activities in skin regeneration, including cell survival, proliferation, and collagen enhancement for Human Fibroblast (HFB) degraded by oxidative stress. These results show that the relatively low energy of less than 300 W and an amount of NOx-based reactive nitrogen species (RNS) from plasma discharge of about 3 μL/L were the key factors and that RSCE, of which the antioxidant activity was enhanced by plasma treatment, appeared to be a major contributor to the protective effect of HFB against oxidative stress. Plasma-treated RSCE induced excellent anti-aging properties by stimulating HFB to promote collagen synthesis, thereby promoting skin regeneration. These properties can protect the skin from various oxidative stresses. This study demonstrates that plasma-treated extracts of stem cells derived from rice-seed embryos have an excellent regenerative effect on aging-treated HFB. Our results demonstrate the potential utility of plasma-treated RSCE as a skin anti-aging agent in cosmeceutical formulations for the first time.

Effective penetration into cells, or binding to cell membranes is an essential property of an effective nanoparticle drug delivery system (DDS). Nanoparticles are generally internalized through active transport mechanisms such as apoptosis, and cargo can be released directly into the cytoplasm. A metal–organic framework (MOF) is a network structure consisting of metal clusters connected by organic linkers with high porosity; MOFs provide a desirable combination of structural features that can be adjusted with large cargo payloads, along with Cu, Co, and Zn-MOFs, which have the chemical stability required for water-soluble use. Bioactive MOFs containing copper, cobalt, and zinc were prepared by modifying previous methods as therapeutic drugs. Their structures were characterized via PXRD, single-crystal crystallographic analysis, and FT-IR. The degradability of MOFs was measured in media such as deionized water or DPBS by PXRD, SEM, and ICP-MS. Furthermore, we investigated the anticancer activity of MOFs against the cell lines SKOV3, U87MG, and LN229, as well as their biocompatibility with normal fibroblast cells. The results show that a nanoporous 3D Cu-MOF could potentially be a promising candidate for chemoprevention and chemotherapy.

Non-thermal biocompatible plasma (NBP) was considered as an efficient tool in tissue engineering to modify the surface of biomaterials. Three-dimensional chitosan scaffolds have been extensively used in different ways because it holds some remarkable properties, including biodegradability and biocompatibility. In this study, we evaluated the osteogenic potential of NBP-treated chitosan scaffolds using two different plasma sources: a dielectric barrier discharge (NBP-DBD) and a soft jet (NBP-J). The surface modification of the scaffold was evaluated using scanning electron microscopy. For osteogenic differentiation of cells, proliferation and differentiation were tested by using bone marrow-derived stem cells (BMSCs). We observed that cell viability using NBP-DBD and NBP-J treated chitosan scaffolds yielded significant improvements in cell viability and differentiation. The results obtained with MTT and live/dead assays showed that NBP-modified scaffold increases cell metabolic by MTT assay and live/dead assay. It also observed that the NBP treatment is more effective at 5 min with DBD and was selected for further investigations. Enhanced osteogenic differentiation was observed using NBP-treated scaffolds, as reflected by increased alkaline phosphatase activity. Our findings showed that NBP is an innovative and beneficial tool for modifying chitosan scaffolds to increase their activity, making them suitable as biocompatible materials and for bone tissue engineering.

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.

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.

Pelvic organ prolapse (POP) is a chronic disorder that affects quality of life in women. Several POP treatments may be accompanied by abrasion, constant infection, and severe pain. Therefore, new treatment methods and improvements in current treatments for POP are required. Non-thermal atmospheric-pressure plasma is a rising biomedical therapy that generates a mixed cocktail of reactive species by different mechanisms. In this study, we applied a cylinder-type dielectric barrier discharge plasma device to create a plasma-treated liquid (PTL). The PTL was added to primary cultured human uterosacral ligament fibroblast (hUSLF) cells from POP patients at each stage. Surprisingly, treatment with diluted PTL increased hUSLF cell viability but decreased ovarian cancer cell viability. PTL also decreased cell apoptosis in hUSLF cells but increased it in SKOV3 cells. Our results suggest that PTL protects hUSLF cells from cell apoptosis by controlling the p53 pathway and improves cell viability, implying that PTL is a promising application for POP therapy.

Abstract Although various oral pathogens are inactivated by non-thermal atmospheric pressure plasma (NTAPP), the in vivo effects of NTAPP are poorly understood. The first aim of this study was to examine the antibacterial activity of microwave-pulsed NTAPP against Staphylococcus aureus in artificial saliva to mimic oral environmental conditions. The second aim was to determine the influence of microwave-pulsed NTAPP on human gingival fibroblasts (HGFs). The microwave-pulsed NTAPP reduced bacterial viability (as measured by colony forming units [CFU]) to a greater extent in artificial saliva than in saline. Extending the post-treatment incubation time increased bacterial inactivation in artificial saliva compared to saline. HGFs viability was unaffected by microwave-pulsed NTAPP for bacterial inactivation. Rather, HGFs proliferation increased after a 5-min microwave-pulsed NTAPP. Less tumor necrosis factor alpha was released by microwave-pulsed NTAPP-treated HGFs stimulated with lipopolysaccharide (LPS) than by untreated, LPS-stimulated HGFs; thus, plasma appeared to suppress the inflammatory response. Our study suggests that microwave-pulsed NTAPP may have stronger in vivo antibacterial activity than in vitro activity, and that microwave-pulsed NTAPP may have the additional advantage of suppressing gingival inflammatory responses.

Non-thermal atmospheric-pressure biocompatible plasma (NBP) has diverse functions such as surface treatment, and cleaning and decomposing organic matter. Few commercially available devices use plasma to sterilize and disinfect the air and surfaces. We commercialize a new plasma sterilizer that can eradicate viruses, bacteria, etc., using NBP with a compact setup. The hydroxyl (OH) radical species concentration inside the dielectric-barrier discharge (DBD) is estimated from the equation reduced by R. Sankaranarayanan, which is approximately 9.78 × 1015 cm−3. The new plasma sterilizer with water droplets developed in this work exhibits excellent sterilization properties, with the OH radical concentration being approximately 30 times higher than that obtained in other types of atmospheric-pressure DBD devices in air saturated with vapor.

Glioblastoma multiforme (GBM) is a highly malignant and rapidly advancing astrocytic brain tumor in adults. Current therapy possibilities are chemotherapy, surgical resection, and radiation. The complexity of drug release through the blood-brain barrier, tumor reaction to chemotherapy, and the inherent resistance of tumor cells present challenges. New therapies are needed for individual use or combination with conventional methods for more effective treatment and improved survival for patients. GBM is difficult to treat because it grows quickly, spreads finger-shaped tentacles, and creates an irregular margin of normal tissue surrounding the tumor. Non-thermal biocompatible plasma (NBP) has recently been shown to selectively target cancer cells with minimal effects on regular cells, acting by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS). We applied a soft jet plasma device with a syringe shape to U87 MG cells and astrocytes. Our results show that NBP-J significantly inhibits cell proliferation and changes morphology, induces cell cycle arrest, inhibits the survival pathway, and induces apoptosis. Our results indicate that NBP-J may be an efficient and safe clinical device for brain cancer therapy.

Purpose The differentiation properties of stem cells are not yet fully understood due to their close association with multiple environmental and extrinsic factors. This study investigates the differentiation properties of mesenchymal stem cells (MSCs) and correlates them with their intrinsic mechanical properties. Methods A total of 3 different types of MSCs, namely bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UCSCs), and adipose-derived MSCs (ADSCs) were evaluated. These 3 MSCs were individually differentiated into adipocytes and osteoblasts for 3 weeks. The mechanical properties of the MSCs and differentiated cells were determined by atomic force microscopy. Results ADSCs showed the greatest ability to differentiate into adipocytes, followed by BMSCs and UCSCs. While UCSCs differentiated readily into osteoblasts, BMSCs and ADSCs were less likely to undergo this differentiation. UCSCs were the “hardest” cells, while ADSCs were the “softest.” The cells differentiated from “hard” MSCs were stiffer than the cells differentiated from “soft” MSCs, irrespective of lineage specification. Conclusions The differentiation ability of MSCs and the mechanical properties of the differentiated cells were closely linked. However, there were no significant correlations regarding changes in the mechanical properties between the nuclear region and the cytoplasm during differentiation.

Atmospheric-pressure A r plasma jets are known to be detrimental to Cordyceps pruinosa spores. However, it is not clear what kinds of reactive species are more effective with regard to fungal cell death. Herein, we study which reactive species plays pivotal roles in the death of fungal spores using an electric shock-free, atmospheric-pressure air plasma jet, simply called soft plasma jet. Plasma treatment significantly reduced the spore viability and damaged fungal DNA. As observed from the circular dichroism spectra, scanning electron microscope images, and flow cytometric measurements, cell wall integrity was decreased by reactive oxygen and nitrogen species (RONS) from the plasma itself and the plasma-activated water. Consequently, degradation of the spore cell wall allows RONS from the plasma to reach the intracellular components. Such plasma-induced intracellular RONS can attack spore DNA and other intracellular components, as confirmed by electrophoresis analysis and phosphorylated histone measurement. In addition, weakening of the spore cell wall allowed for the loss of intracellular components, which can lead to cell death. Plasma radicals were investigated by measuring the optical emission spectrum of the soft plasma jet, and intracellular reactive oxygen species were confirmed by measuring the fluorescence of 2′, 7′-dichlorodihydrofluorescein-diacetate ( H 2 D C F - D A )-stained spores. The soft plasma jet generated considerable amounts of H 2 O 2 and N O x but a very small number of O H radicals as compared to the atmospheric-pressure A r plasma jet; this indicates that plasma-induced long-lived reactive species ( H 2 O 2 and N O x ) play an important role in the weakening of spore cell walls and cell death.

This article [1] has been retracted by the authors because, contrary to the statement in the article, ethical approval was not obtained to conduct this study.

The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy.

The death process of Candida albicans was investigated after treatment with the antifungal agents flucytosine and amphotericin B by assessing morphological and biophysical properties associated with cell death. C. albicans was treated varying time periods (from 6 to 48 hours) and examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM). SEM and AFM images clearly showed changes in morphology and biophysical properties. After drug treatment, the membrane of C. albicans was perforated, deformed, and shrunken. Compared to the control, C. albicans treated with flucytosine was softer and initially showed a greater adhesive force. Conversely, C. albicans treated with amphotericin B was harder and had a lower adhesive force. In both cases, the surface roughness increased as the treatment time increased. The relationships between morphological changes and the drugs were observed by AFM clearly; the surface of C. albicans treated with flucytosine underwent membrane collapse, expansion of holes, and shrinkage, while the membranes of cells treated with amphotericin B peeled off. According to these observations, the death process of C. albicans was divided into 4 phases, CDP(0), CDP(1), CDP(2), and CDP(4), which were determined based on morphological changes. Our results could be employed to further investigate the antifungal activity of compounds derived from natural sources.

BACKGROUND: We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. METHODOLOGY/PRINCIPAL FINDINGS: We showed that PO (IC(50) = 17.3 microg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC(50) over 200 microg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 microg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 microg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells.