Pharmacologic or genetic interference with atrogene signaling protects from glucocorticoid-induced musculoskeletal and cardiac disease.

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart, the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of Vitamin D receptor (VDR) signaling with the VDR ligands 1,25D3 (calcitriol, 1,25-dihydroxyvitamin D3) or ED (eldecalcitol, 2ß-(3-hydroxypropyloxy)-1,25-dihydroxyvitamin D3) prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of three tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ∆RING mice afforded temporary or sustained protection from GC excess in bone, or skeletal and heart muscle, respectively. We conclude that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the three tissues.

A rare report of H-partially deficient, non-secretor phenotype from India. An Ah like the rèunion and unlike a Para Bombay-Clarifying misinterpretations.

BACKGROUND: H-deficient phenotypes are classified as H-deficient non- secretors (Bombay Oh), H-deficient secretors (Para Bombay), and H-partially deficient non-secretors (O h reunion, Ah and Bh, ABh). REPORT: We report the first case of H-partially deficient non-secretor- the Ah phenotype from India. What makes this report interesting is that they do not fit into the Bombay, or the Para Bombay series of H-deficient phenotypes and these partially deficient non-secretors were exclusively found on Réunion Island, off the East Coast of Africa in 1982. These reunion type phenotypes have not been reported since then and may lead to misinterpretations and confusions when encountered in the current existing laboratory settings especially in the low income (LIC's) and low middle income (LMIC's) countries like our own. Moreover, literature from LMIC and LIC incorrectly uses Ah/Bh for parabombay phenotypes. CONCLUSIONS: H-deficient phenotypes are rare, challenging to identify and assign correct notations. Hence, we have highlighted characteristic differences between H-deficient phenotypes and illustrated a diagnostic laboratory approach to correctly identify and assign notations to them especially in the resource constrained settings.

Extended blood group phenotyping of donors from the lower and middle Himalayan region of Uttarakhand India: A pilot study.

BACKGROUND: The state of Uttarakhand, bordering countries such as Tibet and Nepal, is a multi-ethnic region. Further, erythrocyte alloimmunization may arise from the incompatibility of major and/or minor blood groups between ethnically diverse donors and recipients. We aimed to screen Uttarakhand blood donors (UBDs) for extended phenotyping of their erythrocytes serologically. METHODS: This prospective cross-sectional analysis involved all UBD samples collected at the blood centre of our tertiary-care hospital. Samples were obtained over 9 months (Mar'22 to Nov'22). Donors who were O-typed, DAT-negative and non-reactive for TTI markers were processed further for serological testing using the column agglutination technique utilizing 21 different monoclonal antisera (Ortho diagnostics Pvt ltd, Mumbai India). The research was financially aided by UCOST, Uttarakhand, Government of India. RESULTS: Of the 5,407 blood samples collected, the total number of O-typed samples collected was 1622. Of these 1622, 329 (20.2 %) O-typed samples were selected based on our inclusion criteria and hence further phenotyped. Amongst these 329 UBDs, the average age was 32.7 ± 9.32 (18-52) years and the male-to-female ratio was (M: F = 12:1). The prevalence of high- and low-frequency blood antigens in our study was Rh (D 96.6 %, C 84.8 %, c 63.5 %, E 27.9 % and e 92 %), Lewis (Lea 6.3 %, Leb 31.9 %), Kidd (Jka 87.8 %, Jkb 63.2 %), Kell (K 1.8 %, k 96.3 %) and Duffy (Fya 63.5 %, Fyb 10.6 %). And in the MNS system we received 21.2 % as M, 10.9 % N, 37 % S and 51.3 % as s respectively. We also identified some very rare minor antigens such as Dia 1.8 %, Ina 1.8 %, Cw 0.6 % and, 1.2 % Mur positive donors, which are not common in our population, as per the published literature. Moreover, we also identified one Bombay blood phenotype (Oh) in one of our UBD recruits. CONCLUSION: To sum up, practically with the outcome of this research, we were also able to identify rare phenotypes among the local people and a rare blood donor registry was created. This repository shall also come in use for our multi-transfused patients having different oncological and haematological ailments.

Evaluation of Clinical and Radiographic Findings among Patients with Traumatic Dental Injuries Seeking Delayed Treatment.

BACKGROUND: Time elapsed between trauma and treatment greatly influences the prognosis of traumatic dental injuries (TDIs). The aim of this study was to analyze clinical and radiographic findings related to complications of TDIs among patients seeking delayed treatment of such injuries. MATERIALS AND METHODS: 123 permanent teeth with a history of previous TDIs were included in the study. Clinical findings analyzed were the type of fracture, type and number of injured teeth, crown discoloration, and pulpal status of the injured tooth (pulpal diagnosis). The radiographic findings analyzed included pulp canal obliteration (PCO), root resorption (RR), and periapical radiolucency (PR). Statistical analysis included descriptive analysis. RESULTS: Tooth discoloration was the most common presenting complaint (53.65%), while fall (48.78%) was the most frequent cause of trauma. The range of time duration between trauma and presentation for treatment was 5 months to 30 years (average time 12.82 years). Pulp necrosis (PN) was the most common complication (90.24%). Almost half of the teeth with PN had fracture injury and discoloration along with a high frequency of PR (78.37%). Even teeth with a normal appearance were found to have a high incidence of PN (76.92%) and PR (53.84%). The crown discoloration was the second most frequent finding (48.78%). Many teeth (41.66%) with vital pulp were also discolored. Most of the teeth (79.31%) with yellowish discoloration and all teeth with brownish discoloration were nonvital. A high frequency of PN (90%) and PR (78.33%) was found in teeth with discoloration. PR was the most common radiographic finding (69.10%), while PCO and RR were observed in 17.88% and 21.13% of teeth, respectively. CONCLUSION: The findings of this study support the fact that delayed treatment of TDIs leads to increased complications. PN was the most common complication followed by tooth discoloration, RR, and PCO among patients seeking delayed treatment after TDIs.

Mapping of Translocator Protein (18 kDa) in Peripheral Sterile Inflammatory Disease and Cancer through PET Imaging.

Positron emission tomography (PET) imaging of the translocator 18 kDa protein (TSPO) with radioligands has become an effective means of research in peripheral inflammatory conditions that occur in many diseases and cancers. The peripheral sterile inflammatory diseases (PSIDs) are associated with a diverse group of disorders that comprises numerous enduring insults including the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system. TSPO has recently been introduced as a potential biomarker for peripheral sterile inflammatory diseases (PSIDs). The major critical issue related to PSIDs is its timely characterization and localization of inflammatory foci for proper therapy of patients. As an alternative to metabolic imaging, protein imaging expressed on immune cells after activation is of great importance. The five transmembrane domain translocator protein-18 kDa (TSPO) is upregulated on the mitochondrial cell surface of macrophages during inflammation, serving as a potential ligand for PET tracers. Additionally, the overexpressed TSPO protein has been positively correlated with various tumor malignancies. In view of the association of escalated TSPO expression in both disease conditions, it is an immensely important biomarker for PET imaging in oncology and PSIDs. In this review, we summarize the most outstanding advances on TSPO-targeted PSIDs and cancer in the development of TSPO ligands as a potential diagnostic tool, specifically discussing the last five years.

Cold plasma seed priming modulates growth, redox homeostasis and stress response by inducing reactive species in tomato (Solanum lycopersicum).

Seed germination and vegetative growth are two important plant growing stages that are vulnerable to physical and biological stress. Improvement in crop germination potential and seedling growth rate generally leads to high crop productivity. Cold plasma is a promising technology used to improve seed germination and growth. Structural changes on tomato seed surface exposed with cold air plasma jet for a different time period (1 min, 5 min, 10 min) was examined by SEM. For in-depth study, different physiological parameter such as seed germination and seedling growth, biochemical parameter such as reactive species status, antioxidants and phytohormone, and molecular analysis of various gene expression was also evaluated. Drought stress tolerance potential of cold plasma primed tomato seedling was also examined under 30% PEG stress. Cold plasma seed priming modulates tomato seed coat and improves the germination efficiency. It also induces growth, antioxidants, phytohormone, defense gene expression, and drought stress tolerance potential of tomato seedling. Cold plasma seeds priming augment the reactive species at a molecular level within seedlings, which changes the biochemistry and physiological parameters of plants by inducing different cellular signaling cascades.

Cold Atmospheric Plasma as a Novel Therapeutic Tool for the Treatment of Brain Cancer.

BACKGROUND: Studies from the past few years revealed the importance of Cold Atmospheric Plasma (CAP) on various kinds of diseases, including brain cancers or glioblastoma (GBM), and hence coined a new term 'Plasma Medicine' in the modern world for promising therapeutic approaches. Here, we focus on the efficacy of CAP and its liquid derivatives on direct interactions or with specific nanoparticles to show pivotal roles in brain cancer treatment. METHOD: In the present review study, the authors studied several articles over the past decades published on the types of CAP and its effects on different brain cancers and therapy. RESULTS: A growing body of evidence indicates that CAP and its derivatives like Plasma Activated Media/ Water (PAM/PAW) are introduced in different kinds of GBM. Recent studies proposed that CAP plays a remarkable role in GBM treatment. To increase the efficacy of CAP, various nanoparticles of different origins got specific attention in recent times. In this review, different strategies to treat brain cancers, including nanoparticles, are discussed as enhancers of CAP induced targeted nanotherapeutic approach. CONCLUSION: CAP treatment and its synergistic effects with different nanoparticles hold great promise for clinical applications in early diagnosis and treatment of GBM treatment. However, results obtained from previous studies were still in the preliminary phase, and there must be a concern over the use of optimal methods for a dosage of CAP and nanoparticles for complete cure of GBM.

Plant Disease Control by Non-Thermal Atmospheric-Pressure Plasma.

Disease stresses caused by pathogenic microorganisms are increasing, probably because of global warming. Conventional technologies for plant disease control have often revealed their limitations in efficiency, environmental safety, and economic costs. There is high demand for improvements in efficiency and safety. Non-thermal atmospheric-pressure plasma has demonstrated its potential as an alternative tool for efficient and environmentally safe control of plant pathogenic microorganisms in many studies, which are overviewed in this review. Efficient inactivation of phytopathogenic bacterial and fungal cells by various plasma sources under laboratory conditions has been frequently reported. In addition, plasma-treated water shows antimicrobial activity. Plasma and plasma-treated water exhibit a broad spectrum of efficiency in the decontamination and disinfection of plants, fruits, and seeds, indicating that the outcomes of plasma treatment can be significantly influenced by the microenvironments between plasma and plant tissues, such as the surface structures and properties, antioxidant systems, and surface chemistry of plants. More intense studies are required on the efficiency of decontamination and disinfection and underlying mechanisms. Recently, the induction of plant tolerance or resistance to pathogens by plasma (so-called "plasma vaccination") is emerging as a new area of study, with active research ongoing in this field.

Cold Atmospheric Plasma and Silymarin Nanoemulsion Activate Autophagy in Human Melanoma Cells.

BACKGROUND: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. METHODS: The temperature and pH of the media, along with the cell number, were evaluated. The intracellular glucose level and PI3K/mTOR and EGFR downstream pathways were assessed. Autophagy-related genes, related transcriptional factors, and autophagy induction were estimated using confocal microscopy, flow cytometry, and ELISA. RESULTS: CAP treatment increased the temperature and pH of the media, while its combination with SN resulted in a decrease in intracellular ATP with the downregulation of PI3K/AKT/mTOR survival and RAS/MEK transcriptional pathways. Co-treatment blocked downstream paths of survival pathways and reduced PI3K (2 times), mTOR (10 times), EGFR (5 times), HRAS (5 times), and MEK (10 times). CAP and SN co-treated treatment modulates transcriptional factor expressions (ZKSCAN3, TFEB, FOXO1, CRTC2, and CREBBP) and specific genes (BECN-1, AMBRA-1, MAP1LC3A, and SQSTM) related to autophagy induction. CONCLUSION: CAP and SN together activate autophagy in G-361 cells by activating PI3K/mTOR and EGFR pathways, expressing autophagy-related transcription factors and genes.

Cold Atmospheric Plasma-Activated Water Irrigation Induces Defense Hormone and Gene expression in Tomato seedlings.

Plants are very vulnerable to pathogen attacks and environmental stress as they are exposed to harsh environments in natural conditions. However, they have evolved a self-defense system whereby reactive oxygen and nitrogen species (RONS) act as double-edged swords by imposing (at higher concentration) and mitigating (at lower concentration) environmental stress. Cold plasma is emerging as a feasible option to produce a variety of RONS in a controlled manner when amalgamate with water. Cold plasma activated/treated water (PAW) contains a variety of RONS at concentrations, which may help to activate the plant's defense system components. In the present study, we examine the effect of cold atmospheric-air jet plasma exposure (15 min, 30 min, and 60 min) on the water's RONS level, as well as the impact of PAW irrigation, (assigned as 15PAW, 30PAW, and 60PAW) on tomato seedlings growth and defense response. We found that PAW irrigation (priming) upregulate seedlings growth, endogenous RONS, defense hormone (salicylic acid and jasmonic acid), and expression of key pathogenesis related (PR) gene. 30 min PAW contains RONS at concentrations which can induce non-toxic signaling. The present study suggests that PAW irrigation can be beneficial for agriculture as it modulates plant growth as well as immune response components.

Cold atmospheric plasma and silymarin nanoemulsion synergistically inhibits human melanoma tumorigenesis via targeting HGF/c-MET downstream pathway.

BACKGROUND: Recent studies claimed the important role of cold atmospheric plasma (CAP) with nanotechnology in cancer treatments. In this study, silymarin nanoemulsion (SN) was used along with air CAP as therapeutic agent to counter human melanoma. METHODS: In this study, we examined the combined treatment of CAP and SN on G-361 human melanoma cells by evaluating cellular toxicity levels, reactive oxygen and nitrogen species (RONS) levels, DNA damage, melanoma-specific markers, apoptosis, caspases and poly ADP-ribose polymerase-1 (PARP-1) levels using flow cytometer. Dual-treatment effects on the epithelial-mesenchymal transition (EMT), Hepatocyte growth factor (HGF/c-MET) pathway, sphere formation and the reversal of EMT were also assessed using western blotting and microscopy respectively. SN and plasma-activated medium (PAM) were applied on tumor growth and body weight and melanoma-specific markers and the mesenchymal markers in the tumor xenograft nude mice model were checked. RESULTS: Co-treatment of SN and air CAP increased the cellular toxicity in a time-dependent manner and shows maximum toxicity at 200 nM in 24 h. Intracellular RONS showed significant generation of ROS (< 3 times) and RNS (< 2.5 times) in dual-treated samples compared to control. DNA damage studies were assessed by estimating the level of γ-H2AX (1.8 times), PD-1 (> 2 times) and DNMT and showed damage in G-361 cells. Increase in Caspase 8,9,3/7 (> 1.5 times), PARP level (2.5 times) and apoptotic genes level were also observed in dual treated group and hence blocking HGF/c-MET pathway. Decrease in EMT markers (E-cadherin, YKL-40, N-cadherin, SNAI1) were seen with simultaneously decline in melanoma cells (BRAF, NAMPT) and stem cells (CD133, ABCB5) markers. In vivo results showed significant reduction in SN with PAM with reduction in tumor weight and size. CONCLUSIONS: The use of air CAP using µ-DBD and the SN can minimize the malignancy effects of melanoma cells by describing HGF/c-MET molecular mechanism of acting on G-361 human melanoma cells and in mice xenografts, possibly leading to suitable targets for innovative anti-melanoma approaches in the future.

Biological and medical applications of plasma-activated media, water and solutions.

Non-thermal atmospheric pressure plasma has been proposed as a new tool for various biological and medical applications. Plasma in close proximity to cell culture media or water creates reactive oxygen and nitrogen species containing solutions known as plasma-activated media (PAM) or plasma-activated water (PAW) - the latter even displays acidification. These plasma-treated solutions remain stable for several days with respect to the storage temperature. Recently, PAM and PAW have been widely studied for many biomedical applications. Here, we reviewed promising reports demonstrating plasma-liquid interaction chemistry and the application of PAM or PAW as an anti-cancer, anti-metastatic, antimicrobial, regenerative medicine for blood coagulation and even as a dental treatment agent. We also discuss the role of PAM on cancer initiation cells (spheroids or cancer stem cells), on the epithelial mesenchymal transition (EMT), and when used for metastasis inhibition considering its anticancer effects. The roles of PAW in controlling plant disease, seed decontamination, seed germination and plant growth are also considered in this review. Finally, we emphasize the future prospects of PAM, PAW or plasma-activated solutions in biomedical applications with a discussion of the mechanisms and the stability and safety issues in relation to humans.

An in vivo comparison of accuracy of two electronic apex locators in determining working length using stainless steel and nickel titanium files.

PURPOSE: A key factor affecting the success of endodontic treatment is correct determination of root canal working length (WL). The purpose of this in vivo study was to compare the accuracy of Propex II and iPex II electronic apex locator (EAL) in determining the WL under clinical conditions, to that of radiographic working length (RWL) using stainless steel (SS) and nickel-titanium (NiTi) hand files. PATIENTS AND METHODS: Thirty-seven patients, with 60 anterior teeth (60 canals) scheduled for endodontic treatment participated in this study after ethical approval. Electronic working length (EWL) was determined by the Propex II and iPex II according to manufacturer's instructions using SS Hand K-files and NiTi Hand files. RWL was determined after EWL determination. The results obtained with each EAL with SS and NiTi files were compared with RWL. Data was analyzed statistically at a significance level of p < 0.05. Interclass correlation coefficient was calculated. RESULTS: Statistical analysis revealed no significant difference between the EALs, indicating similar accuracies between them with respect to accuracy in determining the WL (p > 0.05). No significant difference was found between the EWL and RWL and between SS and NiTi files for WL determination (p > 0.05) as well. The result also displayed a high intraclass correlation coefficient between the RWL and EWL measurement methods. CONCLUSION: Under the in vivo clinical conditions of this study, both Propex II and iPex II were similar to the RWL determination technique showing high correlation to RWL. Both are clinically acceptable EAL for WL determination and both SS hand K-file and NiTi file can be used interchangeably without compromising the WL during treatment.