Alendronate-functionalized porous nano-crystalsomes mitigate osteolysis and consequent inhibition of tumor growth in a tibia-induced metastasis model.

Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (41.1%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone-targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications.

A hybrid CNN with transfer learning for skin cancer disease detection.

The leading cause of cancer-related deaths worldwide is skin cancer. Effective therapy depends on the early diagnosis of skin cancer through the precise classification of skin lesions. However, dermatologists may find it difficult and time-consuming to accurately classify skin lesions. The use of transfer learning to boost skin cancer classification model precision is a promising strategy. In this work, we proposed a hybrid CNN with a transfer learning model and a random forest classifier for skin cancer disease detection. To evaluate the efficacy of the proposed model, it was verified over two datasets of benign skin moles and malignant skin moles. The proposed model is able to classify images with an accuracy of up to 90.11%. The empirical results and analysis assure the feasibility and effectiveness of the proposed model for skin cancer classification.

Intravenous Iron Therapy in Heart Failure Patients With Iron Deficiency: Benefits, Safety, and Guidelines.

Iron deficiency is a common comorbidity in heart failure (HF) patients, with up to 50% of ambulatory patients with HF affected. Intravenous (IV) iron therapy has emerged as a promising treatment approach for HF patients with concomitant iron deficiency. This review summarizes the current literature on the use of IV iron therapy in HF patients, focusing on its benefits in improving quality of life, and exercise capacity, and reducing HF hospitalizations. However, concerns about the long-term cardiotoxic effects of IV iron, including the risk of iron overload, are also addressed. The review highlights the importance of a balanced approach to iron replacement and provides an overview of the 2022 American College of Cardiology/American Heart Association guidelines, which recommend IV iron therapy for eligible patients. Additionally, the review underscores the need for further research, particularly in HF patients with preserved ejection fraction and acute HF. While IV iron therapy shows promise, questions about its safety and specific formulations remain to be fully addressed.

A Case of µ Heavy and λ Light Chain Amyloidosis in a Patient With Bi-Clonal (IgM κ and λ) Gammopathy Treated With Daratumumab.

Our case report is of an elderly male with a history of IgM κ lymphoplasmacytic lymphoma (LPL) presenting with generalized neuropathy and weakness. Due to his LPL history and worsening renal function, he underwent a renal biopsy revealing the presence of µ heavy and λ light chains, revealing a diagnosis of amyloidosis with unbound heavy & light chains (AHL), a rare type of amyloidosis. His bone marrow biopsy demonstrated κ light chain restriction by flow cytometry and amyloid deposition. The patient's serum had elevated free κ and λ light chains with a free light chain (FLC) ratio of 3.17. Serum immunofixation was positive for IgM κ and λ light chain clones. He completed six cycles of cyclophosphamide, bortezomib, dexamethasone, and rituximab (CyBorD+R), normalizing the FLC ratio. Still, he continued to present with persistently elevated M protein, IgM κ, and λ light chains on immunofixation. Thereafter, daratumumab, a human monoclonal antibody directed against CD38 expressed on myeloma cells was initiated, which led to a negative immunofixation study after two cycles accompanied by a reduction in protein excretion in the urine. The patient achieved a complete hematological response with daratumumab. To date, our case is the only reported µ heavy and λ light chain amyloidosis patient with bi-clonal (IgM κ and λ) gammopathy to be successfully treated with daratumumab.

Initiation of Cancer: The Journey From Mutations in Somatic Cells to Epigenetic Changes in Tissue-resident VSELs.

Multiple theories exist to explain cancer initiation, although a consensus on this is crucial for developing effective therapies. 'Somatic mutation theory' suggests that mutations in somatic cells during DNA repair initiates cancer but this concept has several attached paradoxes. Research efforts to identify quiescent cancer stem cells (CSCs) that survive therapy and result in metastasis and recurrence have remained futile. In solid cancers, CSCs are suggested to appear during epithelial-mesenchymal transition by the dedifferentiation and reprogramming of epithelial cells. Pluripotent and quiescent very small embryonic-like stem cells (VSELs) exist in multiple tissues but remain elusive owing to their small size and scarce nature. VSELs are developmentally connected to primordial germ cells, undergo rare, asymmetrical cell divisions and are responsible for the regular turnover of cells to maintain tissue homeostasis throughout life. VSELs are directly vulnerable to extrinsic endocrine insults because they express gonadal and gonadotropin hormone receptors. VSELs undergo epigenetic changes due to endocrine insults and transform into CSCs. CSCs exhibit genomic instability and develop mutations due to errors during DNA replication while undergoing excessive proliferation and clonal expansion to form spheroids. Thus tissue-resident VSELs offer a connection between extrinsic insults and variations in cancer incidence reported in various body tissues. To conclude, cancer is indeed a stem cell disease with mutations occurring as a consequence. In addition to immunotherapy, targeting mutations, and Lgr5 + organoids for developing new therapeutics, targeting CSCs (epigenetically altered VSELs) by improving their niche and epigenetic status could serve as a promising strategy to treat cancer.

Burden of Anxiety, Depression and Perceived Stress in Patients with Inflammatory Bowel Disease: A Cohort Study from North India.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.

The Role of 5-Fluorouracil in Preventing Recurrence After Enucleation of Odontogenic Keratocyst: A Case Report.

The odontogenic keratocyst (OKC) is known for its high recurrence rate and disputed treatment modalities. In this report, we review the literature elucidating the efficacy of 5-fluorouracil (5-FU) topical application for recurrent OKC, and discuss the management of an OKC with 5-FU after enucleation and a 12-month follow-up. A 38-year-old female patient with an aggressive OKC in the right mandible underwent surgical curettage followed by topical application of 5-FU. Regular follow-up examinations for 12 months (radiological evaluation at three, six, and 12-month intervals) showed no signs of recurrence, with complete resolution of the cystic lesion and gradual bone regeneration. New bone formation was identified in the radiographic follow-up.  This case demonstrates the potential efficacy of topical 5-FU as a promising treatment modality for OKC, warranting further research and validation. A novel and successful therapy for OKC is the topical application of 5-FU. After enucleation, topical application of 5-FU efficiently treats OKC, leading to normal bone healing and regeneration without any adverse local or systemic effects.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

BACKGROUND: Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD. METHODS: A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. RESULTS: Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. CONCLUSION: The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Very Small Embryonic-Like Stem Cells Transform Into Cancer Stem Cells and Are Novel Candidates for Detecting/Monitoring Cancer by a Simple Blood Test.

Cancer continues to remain a "Black Box," as there is no consensus on how it initiates, progresses, metastasizes, or recurs. Many imponderables exist about whether somatic mutations initiate cancer, do cancer stem cells (CSCs) exist, and if yes, are they a result of de-differentiation or originate from tissue-resident stem cells; why do cancer cells express embryonic markers, and what leads to metastasis and recurrence. Currently, the detection of multiple solid cancers through liquid biopsy is based on circulating tumor cells (CTCs) or clusters, or circulating tumor DNA (ctDNA). However, quantity of starting material is usually adequate only when the tumor has grown beyond a certain size. We posit that pluripotent, endogenous, tissue-resident, very small embryonic-like stem cells (VSELs) that exist in small numbers in all adult tissues, exit from their quiescent state due to epigenetic changes in response to various insults and transform into CSCs to initiate cancer. VSELs and CSCs share properties like quiescence, pluripotency, self-renewal, immortality, plasticity, enrichment in side-population, mobilization, and resistance to oncotherapy. HrC test, developed by Epigeneres, offers the potential for early detection of cancer using a common set of VSEL/CSC specific bio-markers in peripheral blood. In addition, NGS studies on VSELs/CSCs/tissue-specific progenitors using the All Organ Biopsy (AOB) test provide exomic and transcriptomic information regarding impacted organ(s), cancer type/subtype, germline/somatic mutations, altered gene expressions, and dysregulated pathways. To conclude, HrC and AOB tests can confirm the absence of cancer and categorize the rest of subjects into low/moderate/high risk of cancer, and also monitor response to therapy, remission, and recurrence.

Low prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease in India.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. METHODS: Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. RESULTS: Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. CONCLUSIONS: Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.

Extremely Active Nano-formulation of Resveratrol (XAR™) attenuates and reverses chemotherapy-induced damage in mice ovaries and testes.

BACKGROUND: Fertility preservation and restoration in cancer patients/survivors is the need of present times when increased numbers of patients get cured of cancer but face infertility as a serious side effect. Resveratrol has beneficial effects on chemoablated ovaries and testes in mice but has failed to enter the clinics because of extremely poor bioavailability. The present study was undertaken to evaluate the protective and curative effects of Extremely active Resveratrol (XAR™)- a nano-formulation of resveratrol with significantly improved bioavailability- on mouse ovary and testis after chemotherapy. Effects of XAR™ and FSH were compared on stimulation of follicle growth in adult mice ovaries. XAR™ (25 mg/kg) was administered for two days prior to chemotherapy to study the protective effects on the mouse gonads. XAR™ was also administered for 14 days post chemoablation to study the regenerative effects. Besides effect on numbers of primordial and growing follicles and spermatogenesis, the effect of XAR™ was also evaluated on the transcripts specific for ovarian/testicular stem/progenitor/germ cells, their proliferation, differentiation, meiosis, and the antioxidant indices. RESULTS: Similar to FSH, XAR™ increased the numbers of primordial follicles (PF) as well as growing follicles. It protected the gonads from the adverse effects of chemotherapy and showed the ability to regenerate non-functional, chemoablated gonads. Besides stimulating follicle growth in adult ovaries similar to FSH, XAR™ also protected the testes from the adverse effects of chemotherapy and improved spermatogenesis. This was accompanied by improved anti-oxidant indices. CONCLUSIONS: The results of the present study potentiate the use of XAR™ in pilot clinical studies to protect gonadal function during oncotherapy and also regenerate non-functional gonads in cancer survivors by improving antioxidant indices and stem cell-based tissue regeneration.

Nanoparticles of naturally occurring PPAR-γ inhibitor betulinic acid ameliorates bone marrow adiposity and pathological bone loss in ovariectomized rats via Wnt/ß-catenin pathway.

AIMS: Postmenopausal osteoporosis is one of the world's biggest yet unnoticed health issues. After ovariectomy, declined estrogen level significantly contributes to the elevation of bone marrow adiposity and bone loss leading to osteoporosis. Therapeutics to prevent osteoporosis addressing various aspects are now in short supply. In this study we made an approach to synthesize nanoparticles of naturally occurring PPAR-γ inhibitor, betulinic acid (BA/NPs) and tested the same in altered bone metabolisms developed after ovariectomy. MAIN METHODS: The osteogenic efficacy of BA/NPs was established in human and rat primary osteoblast cells using qRT-PCR and immunoblot analysis. Furthermore, lineage allocations of multipotent bone marrow stromal cells were evaluated. Various aspects of altered bone metabolism after ovariectomy such as bone marrow adiposity and pathological bone loss were evaluated using µCT and histological assessments. KEY FINDINGS: BA/NPs exert potential osteogenic efficacy by modulating key osteogenic markers such as RUNX2 and BMP2. Mechanistically BA/NPs regulate osteoblastogenesis through Wnt/ß-catenin signaling. Further, BA/NPs showed the potential to inhibit the differentiation of multipotent BMSCs towards adipogenesis while favouring the osteogenic lineage via Wnt/ß-catenin pathway. In the in vivo study, increased bone marrow adiposity was reduced in ovariectomized rats after BA/NPs treatment as assessed by histology and µCT analysis. Loss of bone mineral density as a hallmark of pathological bone loss was also abrogated by BA/NPs. Furthermore, increased obesity after OVX was also prevented in BA/NPs treated animals. SIGNIFICANCE: Our findings imply that BA/NPs could be used further as a viable drug lead to counteract various pathophysiological challenges after menopause.

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging.

The concept of dedifferentiation and reprogramming of mature somatic cells holds much promise for the three-front "war" against tissue damage, cancer, and aging. It was hoped that reprogramming human somatic cells into the induced pluripotent state, along with the use of embryonic stem cells, would transform regenerative medicine. However, despite global efforts, clinical applications remain a distant dream, due to associated factors such as genomic instability, tumorigenicity, immunogenicity, and heterogeneity. Meanwhile, the expression of embryonic (pluripotent) markers in multiple cancers has baffled the scientific community, and it has been suggested that somatic cells dedifferentiate and "reprogram" into the pluripotent state in vivo to initiate cancer. It has also been suggested that aging can be reversed by partial reprogramming in vivo. However, better methods are needed; using vectors or Yamanaka factors in vivo, for example, is dangerous, and many potential anti-aging therapies carry the same risks as those using induced pluripotent cells, as described above. The present perspective examines the potential of endogenous, pluripotent very small embryonic-like stem cells (VSELs). These cells are naturally present in multiple tissues; they routinely replace diseased tissue and ensure regeneration to maintain life-long homeostasis, and they have the ability to differentiate into adult counterparts. Recent evidence suggests that cancers initiate due to the selective expansion of epigenetically altered VSELs and their blocked differentiation. Furthermore, VSEL numbers have been directly linked to lifespan in studies of long- and short-lived transgenic mice, and VSEL dysfunction has been found in the ovaries of aged mice. To conclude, a greater interest in VSELs, with their potential to address all three fronts of this war, could be the "light at the end of the tunnel."

Quest for Pan-Cancer Diagnosis/Prognosis Ends with HrC Test Measuring Oct4A in Peripheral Blood.

Cancer is a devastating disease whose incidence has increased in recent times and early detection can lead to effective treatment. Existing detection tools suffer from low sensitivity and specificity, and are high cost, invasive and painful procedures. Cancers affecting different tissues, ubiquitously express embryonic markers including Oct-4A, whose expression levels have also been correlated to staging different types of cancer. Cancer stem cells (CSCs) that initiate cancer are possibly the 'transformed' and pluripotent very small embryonic-like stem cells (VSELs) that also express OCT-4A. Excessive self-renewal of otherwise quiescent, pluripotent VSELs in normal tissues possibly initiates cancer. In an initial study on 120 known cancer patients, it was observed that Oct-4A expression in peripheral blood correlated well with the stage of cancer. Based on these results, we developed a proprietary HrC scale wherein fold change of OCT-4A was linked to patient status - it is a numerical scoring system ranging from non-cancer (0-2), inflammation (>2-6), high-risk (>6-10), stage I (>10-20), stage II (>20-30), stage III (>30-40), and stage IV (>40) cancers. Later the scale was validated on 1000 subjects including 500 non-cancer and 500 cancer patients. Ten case studies are described and show (i) HrC scale can detect cancer, predict and monitor treatment outcome (ii) is superior to evaluating circulating tumor cells and (iii) can also serve as an early biomarker. HrC method is a novel breakthrough, non-invasive, blood-based diagnostic tool that can detect as well as classify solid tumors, hematological malignancies and sarcomas, based on their stage.

Benzofuran pyran compound rescues rat and human osteoblast from lipotoxic effect of palmitate by inhibiting lipid biosynthesis and promoting stabilization of RUNX2.

Obesity and ageing increases bone marrow fat which in turn is associated with lower bone mass. Marrow adipocytes by secreting cytokines, adipokines and free fatty acids change the bone marrow milieu and thus the number of osteoblasts. Palmitate is the common saturated fatty acid, an unavoidable ingredient we consume with food, which kindles cell apoptosis. Compound 4e is osteogenic in nature. We examine the effect of compound 4e in palmitate induced lipotoxicity in rat osteoblasts. Design of benzofuran Pyran hybrid compound (4e) was found to be effective in inhibiting palmitate induced cell apoptosis. In this study an in vitro model of palmitate was contrived. Anti-apoptotic effect of compound 4e was assessed by Annexin/PI and LDH (Lactate dehydrogenase) assay. Compound 4e also increased osteoblast differentiation and mineralization. It also increased expression of osteogenic markers (RUNX2 and BMP2), assessed by Real time PCR and immunofluorescence, which was impeded by palmitate. Acetyl Co-Carboxylase (ACC) and Fatty acid synthase (FAS), two prominent mediators of lipid biosynthesis were increased by palmitate exposure. Compound 4e modulated lipid biosynthesis by inhibiting ACC and FAS as reflected visually and after quantification of less lipid droplet formation suggesting that 4e is osteogenic and simultaneously anti-lipotoxic.

Glucocorticoid aggravates bone micro-architecture deterioration and skeletal muscle atrophy in mice fed on high-fat diet.

High fat diet (HFD) induced obesity has deleterious effect on bone micro-architecture and is associated with low-grade chronic inflammation. Exogenous glucocorticoids (GC) are used to treat inflammatory conditions but with concomitant adverse effect on musculoskeletal system. This study aims to highlight the effect of exogenous GCs on musculoskeletal system in mice fed on HFD. Adult BALB/c mice were fed either normal chow or high fat diet and were exogenously administered with GC for 10 weeks. At the end of the study, animals were autopsied and bone, muscle, serum samples were collected for micro-CT, gene expression and histological study. HFD induced obesity resulted in deterioration in bone micro-architecture predominant in trabecular region of long bones and was significantly amplified with GC administration. Approximately, 37% and 25% loss in femoral and tibial bone volume was observed in obese animals with exogenous GC. Further, deteriorating bone pathology was apparent from reduced bone mineral density (BMD) and bone strength parameter which was correlated to alteration in osteoblast and adipocytes pool of cells in bone marrow. Transcriptional analysis of osteoblast marker genes, bone morphogenetic protein 2 (BMP-2), osteocalcin (OCN) exhibited decreased formation. Moreover, similar degeneration was observed in skeletal muscle physiology with stimulation in muscle atrophy genes atrogin-1, muscle ring finger motif-1 (MuRF-1) and inflammatory markers accompanied with intra-myocellular lipid accumulation. Thus, our results showed that detrimental effect of GC on bone and skeletal muscle is aggravated with HFD, attributed to alteration in bone marrow cell population and skeletal muscle atrophy.

Stem Cells and Progenitors in Human Peripheral Blood Get Activated by Extremely Active Resveratrol (XAR™).

Resveratrol generated enormous interest as it improved functions of multiple organs and could delay aging in animal models. However, basic mechanism of action was not understood and due to poor bioavailability, it has failed to enter the market. A highly active nano-formulation of resveratrol (XAR™) with enhanced bioavailability is now available. Present study was undertaken to evaluate its effects on stem cells biology in the human peripheral blood. Twelve healthy participants were enrolled of which five received XAR™, five were age-matched placebo controls and two were 76 and 85 years old. Peripheral blood was processed to study serum profile to monitor cardiac and pancreatic functions and subjected to density gradient centrifugation to enrich pluripotent (VSELs) and adult stem cells that get enriched along with red blood cells and in the Buffy coat respectively on Day 2 and Day 15 after XAR™ treatment. The XAR™ treatment resulted in an increased expression of pluripotency transcripts specific for VSELs (Oct-4A, Nanog and Sox2) on D2; specific transcripts for differentiation in the progenitors including Oct-4, Ikaros, CD14, CD90 on D15, and anti-ageing and tumor suppressor transcripts NAD, SIRT1, SIRT6 and p53 in both stem cells and progenitors. An improvement of cardiac and pancreatic markers in serum profile was also observed on D15. The decline in VSELs numbers with age and beneficial effects of the XAR™ treatment were evident by up-regulation of specific transcripts and on serum profile. XAR™ is a promising molecule that has the potential to activate pluripotent VSELs and tissue committed adult stem cells 'progenitors' resulting in the rejuvenation of various body tissues and for improved, cancer-free health with advanced age.

Long-Wave Infrared (LWIR) Molecular Laser-Induced Breakdown Spectroscopy (LIBS) Emissions of Thin Solid Explosive Powder Films Deposited on Aluminum Substrates.

Thin solid films made of high nitro (NO2)/nitrate (NO3) content explosives were deposited on sand-blasted aluminum substrates and then studied using a mercury-cadmium-telluride (MCT) linear array detection system that is capable of rapidly capturing a broad spectrum of atomic and molecular laser-induced breakdown spectroscopy (LIBS) emissions in the long-wave infrared region (LWIR; ∼5.6-10 µm). Despite the similarities of their chemical compositions and structures, thin films of three commonly used explosives (RDX, HMX, and PETN) studied in this work can be rapidly identified in the ambient air by their molecular LIBS emission signatures in the LWIR region. A preliminary assessment of the detection limit for a thin film of RDX on aluminum appears to be much lower than 60 µg/cm2. This LWIR LIBS setup is capable of rapidly probing and charactering samples without the need for elaborate sample preparation and also offers the possibility of a simultaneous ultraviolet visible and LWIR LIBS measurement.

Anticonvulsant activity of bacopa monniera in rodents / Anticonvulsivante atividade de bacopa monniera em roedores

Bacopa monnieri (L), belonging to the Scrophulariaceae family and commonly known as Brahmi, is well known in India for its CNS activity but its neuropharmacological effect has not yet been explored. In the present study, the antiepileptic effects of the plant were investigated. The ethanolic extract of Bacopa monniera was tested for anticonvulsant activity in albino rats, using different convulsive models. The ethanolic extract of leaves produced significant anticonvulsant activity for all the different models studied. The present study shows a probable mechanism of action similar to that of benzodiazepines (GABA agonist). Thus, these results emphasize the need to diversify by using alternative therapeutic approaches pertaining to herbal medicine, where a single easily available plant may provide solutions to several therapeutic challenges, as observed in the anticonvulsant action of ethanolic extract of B. monniera.

Bacopa monniera, da família Scrophulariaceae, e comumente denominada Brahmi, é bem conhecida na Índia por sua atividade no Sistema Nervoso Central, mas seu efeito neurofarmacológico não foi, ainda, explorado. No presente estudo, investigaram-se os efeitos antiepilépticos da planta. O extrato etanólico da Bacopa monniera foi testado quanto à atividade anticonvulsivante em ratos albinos, utilizando-se diferentes modelos de convulsão. O extrato etanólico das folhas produziu atividade anticonvulsivante significativa para todos os diferentes modelos estudados. O presente estudo mostra provável mecanismo de ação semelhante ao dos benzodiazepínicos (agonista do GABA). Assim sendo, esses resultados enfatizam a necessidade de diversificar, utilizando-se abordagens terapêuticas alternativas da medicina natural, em que uma planta facilmente disponível pode fornecer soluções para vários desafios terapêuticos, como o observado na ação anticonvulsivante do extrato etanólico de Bacopa monniera.

Correlation of mass spectrometry identified bacterial biomarkers from a fielded pyrolysis-gas chromatography-ion mobility spectrometry biodetector with the microbiological gram stain classification scheme.

A pyrolysis-gas chromatography-ion mobility spectrometry (Py-GC-IMS) briefcase system has been shown to detect and classify deliberately released bioaerosols in outdoor field scenarios. The bioaerosols included Gram-positive and Gram-negative bacteria, MS-2 coliphage virus, and ovalbumin protein species. However, the origin and structural identities of the pyrolysate peaks in the GC-IMS data space, their microbiological information content, and taxonomic importance with respect to biodetection have not been determined. The present work interrogates the identities of the peaks by inserting a time-of-flight mass spectrometry system in parallel with the IMS detector through a Tee connection in the GC module. Biological substances producing ion mobility peaks from the pyrolysis of microorganisms were identified by their GC retention time, matching of their electron ionization mass spectra with authentic standards, and the National Institutes for Standards and Technology mass spectral database. Strong signals from 2-pyridinecarboxamide were identified in Bacillus samples including Bacillus anthracis, and its origin was traced to the cell wall peptidoglycan macromolecule. 3-Hydroxymyristic acid is a component of lipopolysaccharides in the cell walls of Gram-negative organisms. The Gram-negative Escherichia coli organism showed significant amounts of 3-hydroxymyristic acid derivatives and degradation products in Py-GC-MS analyses. Some of the fatty acid derivatives were observed in very low abundance in the ion mobility spectra, and the higher boiling lipid species were absent. Evidence is presented that the Py-GC-ambient temperature and pressure-IMS system generates and detects bacterial biochemical information that can serve as components of a biological classification scheme directly correlated to the Gram stain reaction in microorganism taxonomy.