Suppression of MAPK/NF-kB and activation of Nrf2 signaling by Ajugarin-I in EAE model of multiple sclerosis.

Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamate-induced HT22 cells and hydrogen peroxide (H2 O2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach.

Cancer is the leading cause of mortality and morbidity worldwide, and its cases are rapidly increasing every year. Several factors contribute to the development of tumorigenesis. including radiation, dietary lifestyle, smoking, environmental, and genetic factors. The cell cycle is regulated by a variety of molecular signaling proteins. However, when the proteins involved in the cell cycle regulation are altered, cellular growth and proliferation are significantly affected. Natural products provide an important source of new drug development for a variety of ailments. including cancer. Phytosterols (PSs) are an important class of natural compounds reported for numerous pharmacological activities, including cancer. Various PSs, such as ergosterol, stigmasterol, sitosterol, withaferin A, etc., have been reported for their anti-cancer activities against a variety of cancer by modulating the tumor microenvironment via molecular signaling pathways discussed within the article. These signaling pathways are associated with the production of pro-inflammatory mediators, growth factors, chemokines, and pro-apoptotic and anti-apoptotic genes. These mediators and their upstream signaling are very active within the variety of tumors and by modulating these signalings, thus PS exhibits promising anti-cancer activities. However, further high-quality studies are needed to firmly establish the clinical efficacy as well the safety of the phytosterols.

Anti-inflammatory and analgesic potential of leaf extract of Justicia adhatoda L. (Acanthaceae) in Carrageenan and Formalin-induced models by targeting oxidative stress.

Plants are regarded as a valuable and inexpensive source of new drug development, and a variety of plant compounds are now being used in clinical trials to treat a variety of ailments. The goal of this work was to characterize and evaluate the anti-inflammatory and antioxidant effects of Justicia adhatoda L. leaf extract (Acanthaceae). The presence of alkaloids, saponins, tannins, phytosterols, phenols, and proteins in the leaf extract of J. adhatoda was determined using phytochemical screening. While the identification of different compounds in the leaf extract was carried out by HPLC analysis. Similarly, the anti-inflammatory potential of the leaf extract was assessed in Carrageenan and Formalin-induced inflammatory mice models. The phytochemical analysis of the leaf extract indicated a positive test for alkaloids, saponins, tannins, phytosterols, phenols, proteins, and amino acids, while the negative test for carbohydrates, and glycosides, flavonoids, and diterpenes. Moreover, among the detected compounds, gallic acid was found in the highest concentration with a 45.42% composition. The leaf extract showed the highest antibacterial activity against E. coli, while the lowest activity against Listeria was observed. The leaf extract of J. adhatoda revealed promising anti-inflammatory, analgesic, and antioxidants activities both in vitro and in vivo. Similarly, the detected compounds portrayed variable pharmacokinetic as well as binding affinities with the target proteins. In conclusion, the leaf extract exhibited significant antioxidants and antibacterial activities using in vitro assays. Similarly, the extract also revealed promising anti-inflammatory activities in vivo while exhibiting variable Pharmacokinetics and binding affinities towards protein target using computational tools.

Potential applications of PEGylated green gold nanoparticles in cyclophosphamide-induced cystitis.

We investigated the effect of green tea extract PEGylated gold nanoparticles (P-AuNPs) making use of its targeted and sustained drug delivery against cyclophosphamide (CYP)-induced cystitis. AuNPs were synthesized by reduction reaction of gold salts with green tea extract following the concept of green synthesis. Mostly spherical-shaped P-AuNPs were synthesized with an average size of 14.3 ± 3.3 nm. Pre-treatment with P-AuNPs (1, 10 mg/kg, i.p.) before CYP (150 mg/kg, i.p.) challenge suggested its uroprotective properties. P-AuNPs significantly reversed all pain-like behaviours and toxicities produced by CYP resulting in a decreased aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and creatinine level. P-AuNPs increased anti-oxidant system by increasing the level of reduced glutathione, glutathione-S-transferase, catalase and superoxide dismutase, and reduced nitric oxide production in bladder tissue. Additionally, it attenuated hypokalaemia and hyponatremia, along with a decrease in Evans blue content in bladder tissue and peritoneal cavity. CYP-induced bladder tissue damage observed by macroscopic and histological findings were remarkably attenuated by P-AuNPs, along with reduced fibrosis of collagen fibre in bladder smooth muscles shown by Masson's trichrome staining. Additionally, alterations in hematological parameters and clinical scoring were also prevented by P-AuNPs suggesting its uroprotective effect.

Land use and land cover modification and its impact on biodiversity and the ecosystem services in District Kurram, Pakistan / Uso del suelo y modificación de la cobertura terrestre y su impacto en la biodiversidad y los servicios de los ecosistemas en el distrito de Kurram, Pakistán

Modifications of land use and vegetation cover are proceeding faster than ever before in human history, with a considerable reduction in forest cover in biodiversity hotspots. We investigated the land use and vegetation cover changes, their impact on biodiversity in the Kurram District, Pakistan, for 27 years (1989 to 2015). Temporal satellite imagery was processed using a supervised maximum likelihood classification algorithm in ARCGIS 10.1 to elucidate information regarding land use/land cover changes,with conducted structured interviews to obtain the inhabitants' perspectives on their dependence on ecosystems in Kurram, and how their environment is changing. We found that the land under forest cover and rangeland showed a remarkable decrease over the study period. This decline in rangeland and forest cover was a result of the increased of farmland, barren land. The study area is part of a biodiversity, with important medicinal, rare and unique plant species.

Las modificaciones del uso de la tierra y la cobertura vegetal están avanzando más rápido que nunca en la historia de la humanidad, con una reducción considerable de la cobertura forestal en los puntos críticos de biodiversidad. Investigamos el uso de la tierra y los cambios en la cobertura vegetal, su impacto en la biodiversidad en el distrito de Kurram, Pakistán, durante 27 años (1989 a 2015). Las imágenes satelitales temporales se procesaron utilizando un algoritmo de clasificación de máxima verosimilitud supervisada en ARCGIS 10.1 para dilucidar información sobre los cambios en el uso del suelo/cobertura del suelo, con entrevistas estructuradas realizadas para obtener las perspectivas de los habitantes sobre su dependencia de los ecosistemas en Kurram y cómo está cambiando su entorno. Descubrimos que la tierra cubierta por bosques y pastizales mostró una disminución notable durante el período de estudio. Esta disminución en los pastizales y la cubierta forestal fue el resultado del aumento de las tierras de cultivo, tierras estériles. El área de estudio es parte de una biodiversidad, con importantes especies de plantas medicinales, raras y únicas.

Tuberculosis and Diabetes in India: Stakeholder Perspectives on Health System Challenges and Opportunities for Integrated Care.

BACKGROUND: India has a dual burden of tuberculosis (TB) and diabetes mellitus (DM). Integrated care for TB/DM is still in the early phase in the country and can be considerably enhanced by understanding and addressing the challenges identified from stakeholders' perspectives. This study explored the challenges and opportunities at individual, health system and policy level for integrated care of TB/DM comorbidities in India. METHODS: We used an outlier case study approach and conducted stakeholder interviews and focus group discussions with relevant program personnel including field staff and program managers of TB and DM control programs as well as officials of partners in Indian states, Kerala and Bihar. RESULTS: The integrated management requires strengthening the laboratory diagnosis and drug management components of the two individual programs for TB and DM. Focused training and sensitization of healthcare workers in public and private sector across all levels is essential. A district level management unit that coordinates the two vertical programs with a horizontal integration at the primary care level is the way forward. Substantial improvement in data infrastructure is essential to improve decision-making process. CONCLUSION: Bi-directional screening and management of TB/DM comorbidities in India requires substantial investment in human resources, infrastructure, drug availability, and data infrastructure.

A Comparative Antibacterial, Antioxidant, and Antineoplastic Potential of Rauwolfia serpentina (L.) Leaf Extract with Its Biologically Synthesized Gold Nanoparticles (R-AuNPs).

Rauwolfia serpentina (R. serpentina), belonging to the family Apocynaceae, is a renowned medicinal herb for its different pharmacological activities such as antibacterial, antifungal, anti-inflammatory, and antiproliferative characteristics. This study has done a comparative assessment of the antibacterial, antioxidant, and anti-cancer activity of R. serpentina aqueous leaf extract (RSALE) with encapsulated gold nanoparticles (R-AuNPs). The R-AuNPs are prepared so that they are significant in size, monodispersed, and extremely stable. Their characterization was done by numerous parameters, including UV-visible spectroscopy (528 nm), transmission electron microscopy (~17 d. nm), dynamic light scattering (~68 d. nm), and zeta-potential (~-17 mV). Subsequently, a potent antibacterial activity was depicted via RSALE and R-AuNPs when examined by disc diffusion against various Gram-positive and Gram-negative bacterial strains. The obtained zones of inhibition of RSALE (100 mg/mL) were 34 ± 0.1, 35 ± 0.1, 28.4 ± 0.01, and 18 ± 0.01, although those of R-AuNPs (15 mg/mL) were 24.4 ± 0.12, 22 ± 0.07, 20 ± 0.16, and 17 ± 0.3 against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (MTCC 8114), and Streptococcus pyogenes (ATCC 19615), respectively. However, no zone of inhibition was obtained when tested against Proteus vulgaris (MTCC 1771). Furthermore, the obtained MIC values for Staphylococcus aureus were 0.91, 0.61, and 1.15 mg/mL; for Escherichia coli, 0.79, 0.36, and 1.02 mg/mL; for Bacillus subtilis 0.42, 0.27, and 0.474 mg/mL; and for Streptococcus pyogenes, 7.67, 3.86, and 8.5 mg/mL of pure RSALE, R-AuNPs, and Amoxicillin (control), respectively, incorporating that R-AuNPs have been shown to have a 1.4-fold, 2.1-fold, 1.5-fold, and 1.9-fold enhanced antibacterial activity in contrast to pure RSALE tested against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Streptococcus pyogenes, and Proteus vulgaris, respectively. Additionally, an enhanced antioxidant potential was detected in R-AuNPs compared to RSALE evaluated by the 2,2-Diphenyl-1-Picryl Hydrazyl Radical Scavenging (DPPH) Ferric reducing antioxidant power (FRAP) assay. The determined IC 50 values of RSALE and R-AuNPs were 0.131 ± 0.05 and 0.184 ± 0.02 mg/mL, and 0.110 ± 0.1 and 0.106 ± 0.24 mg/mL via the FRAP and DPPH assays, respectively. In addition, the anti-cancer activity against the human cervical cancer (Hela) cell line was evaluated, and the MTT assay results revealed that R-AuNPs (IC50 88.3 µg/mL) had an enhanced anti-cancer potential in contrast to RSALE (171.5 µg/mL). Subsequently, the findings of this study indicated that R. serpentina leaves and their nanoformulation can be used as a potent source for the treatment of the above-mentioned complications and can be used as a possible agent for novel target-based therapies for the management of different ailments.

Anti-allergic activities of Umbelliferone against histamine- and Picryl chloride-induced ear edema by targeting Nrf2/iNOS signaling in mice.

BACKGROUND: The current study was aimed to investigate the anti-allergic activities of the Umbelliferone (UMB) against the acute Histamine and chronic Picryl chloride (PiCl)-induced allergy in mice. UMB is a coumarin derivative (isolated from Angelica decursiva) found in various parts of the plants such as flowers, roots and, stems isolated from the plants of Umbelliferae family. METHODS: The UMB (1, 10, 50 mg/kg) was administered intraperitoneally (i.p) half an h before or 2 h after the induction of allergic ear edema. The acute ear edema was induced by histamine (intradermally, i.d), while the chronic ear edema was induced by painting the PiCl (sensitized with the toluene) on the ear. The antioxidants and oxidative stress markers were assessed. The histological changes were assessed using Hematoxylin and eosin (H and E) and giemsa staining. The immunohistochemistry studies were performed to assess the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and inducible nitric oxide synthase (iNOS). The data was analyzed using one-way ANOVA tests followed by Tukey's test with p < 0.05 was chosen as criteria for statistical significance. RESULTS: UMB treatment markedly reduced the allergic ear edema and ear weight compared to the negative control. Furthermore, the UMB attenuated the oxidative stress markers, while induced the antioxidants enzymes. Similarly, the UMB treatment significantly attenuated the serum immunoglobulin E (IgE) level. The UMB treatment markedly improved the histological parameters using H and E staining and Giemsa staining. The UMB administration induced the Nrf2 expression, while attenuated the iNOS expression. Furthermore, the computational analysis was performed to assess the interaction of the UMB with the various protein targets and to determine the mechanism of interaction with the target proteins. CONCLUSION: In conclusion, the UMB treatment significantly alleviated the allergic symptoms, attenuating the oxidative stress, improved the histological features using in vivo and computational approaches.

Synthesis of Gold Nanoparticles by Using Green Machinery: Characterization and In Vitro Toxicity.

Green synthesis of gold nanoparticles (GNPs) with plant extracts has gained considerable interest in the field of biomedicine. Recently, the bioreduction nature of herbal extracts has helped to synthesize spherical GNPs of different potential from gold salt. In this study, a fast ecofriendly method was adopted for the synthesis of GNPs using fresh peel (aqueous) extracts of Benincasa hispida, which acted as reducing and stabilizing agents. The biosynthesized GNPs were characterized by UV-VIS and Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering. In addition, the in vitro antibacterial and anticancer activities of synthesized GNPs were investigated. The formation of gold nanoparticles was confirmed by the existence of a sharp absorption peak at 520 nm, corresponding to the surface plasmon resonance (SPR) band of the GNPs. TEM analysis revealed that the prepared GNPs were spherical in shape and had an average particle size of 22.18 ± 2 nm. Most importantly, the synthesized GNPs exhibited considerable antibacterial activity against different Gram-positive and Gram-negative bacteria. Furthermore, the biosynthesized GNPs exerted remarkable in vitro cytotoxicity against human cervical cancer cell line, while sparing normal human primary osteoblast cells. Such cytotoxic effect was attributed to the increased production of reactive oxygen species (ROS) that contributed to the damage of HeLa cells. Collectively, peel extracts of B. hispida can be efficiently used for the synthesis of GNPs, which can be adopted as a natural source of antimicrobial and anticancer agent.

Pharmacological evaluation of continentalic acid for antidiabetic potential.

BACKGROUND: Diabetes is a complex endocrine and metabolic disorder. Continentalic acid is a natural drug product found in roots of Aralia continentalis (family Araliaceae), which used in traditional medicine for treatment of rheumatic arthritis, lumbag, lameness, inflammation, gastritis, nephritis and diabetes mellitus. PURPOSE: This study is aim to investigate the continentalic acid anti-diabetic potential. METHODS: In-silico, in-vitro, in-vivo and molecular techniques were used to investigate various effects of continentalic acid by Auto Doc Vina, α-amylase and α-glucosidase inhibitory assay and alloxan-induced diabetes rats model. RESULTS: In-silico results revealed that continentalic acid exhibits binding energy values of - 5 to - 9.3Kcal/mol against selected targets. In-vitro assay showed that continentalic acid caused α-amylase and α-glucosidase enzymes inhibition. In-vivo finding exhibits that continentalic acid (50 mg/kg) decreased blood glucose level, body weight, oral glucose tolerance overload, glycosylated hemoglobin, triglycerides, total cholesterol, low density lipoprotein, aspartate transaminase, aspartate aminotransferase, alkaline phosphate, total bilirubin and increased high density lipoprotein (P < 0.05, P < 0.01, P < 0.001 vs. diabetic control group). In animals pancreas and liver tissues, continentalic acid enhanced glutathione-s-transferase, reduced glutathione, catalase and decreased lipid hydroperoxide level, improved cellular architecture in histopathological examination and decrease expression of inflammatory markers: cyclooxygenase 2, tumor necrosis factor alpha, phosphorylated-nuclear factor kappa B, prostaglandins E2, interleukin-18 and increased heme oxygenase-1, as evidenced in immunohistochemistry and enzyme-linked immunosorbent assay molecular investigations. CONCLUSIONS: This study shows that continentalic acid exhibited binding affinities against the different targets and anti-diabetic action, mediated possibly through α-amylase and α-glucosidase inhibition, anti-hyperlipidemic, hepatoprotection, antioxidant and anti-inflammatory pathways.

Prevalence and determinants of violence against health care in the metropolitan city of Peshawar: a cross sectional study.

BACKGROUND: Violence against healthcare personnel is a major public health problem. Healthcare personnel are at the frontline dealing with people in stressful and unpredictable situations. Therefore, this study was conducted to determine the prevalence and associated factors of violence against health care personnel. METHODS: A cross sectional study was conducted in the district Peshawar. Healthcare personnel from public and private sectors working in both the primary and tertiary levels of healthcare were invited to participate. Violence was assessed through a structured questionnaire previously used in Pakistan and was defined as experiencing and/or witnessing any form of violence in the last 12 months. Mental health was assessed through the General Health Questionnaire. Logistic regression was used to estimate the association of violence against healthcare personnel with psychological distress and demographic characteristics. Data entry and analysis were conducted in STATA 14. RESULTS: A total of 842 healthcare personnel participated in the study. The prevalence of violence experienced and/or witnessed by healthcare personnel in Peshawar was 51%. Verbal violence remained the predominant form of violence and almost half of the healthcare personnel (45%) were exposed to it. A quarter of the respondents (24%) reported physical violence alone or in combination with other forms of violence. In almost two third of the incidents the perpetrators were either attendants, relatives or the patients. The emergency unit and wards within healthcare facilities were the most common places where violent events took place. The major factors responsible for the violent incidents were communication failure, unreasonable expectations and perceived substandard care. No uniform policy/procedure existed to manage the incidents and the healthcare personnel adopted different responses in the wake of violent events targeting health care. Working in public healthcare facilities and having a larger number of co-workers/colleagues significantly increased the risk of violence in the healthcare settings while being a paramedic significantly reduced the risk as compared to physicians. CONCLUSIONS: Violence against healthcare personnel is a serious public health issue and the prevalence is quite high. A holistic effort is needed by all stakeholders including healthcare community, the administration, lawmakers, law enforcement, civil society, and international organizations.

Vitamin D and its therapeutic relevance in pulmonary diseases.

Vitamin D is customarily involved in maintaining bone and calcium homeostasis. However, contemporary studies have identified the implication of vitamin D in several cellular processes including cellular proliferation, differentiation, wound healing, repair and regulatory systems inclusive of host defence, immunity, and inflammation. Multiple studies have indicated corelations between low serum levels of vitamin D, perturbed pulmonary functions and enhanced incidences of inflammatory diseases. Almost all of the pulmonary diseases including acute lung injury, cystic fibrosis, asthma, COPD, Pneumonia and Tuberculosis, all are inflammatory in nature. Studies have displayed strong inter-relations with vitamin D deficiency and progression of lung disorders; however, the underlying mechanism is still unknown. Vitamin D has emerged to possess inhibiting effects on pulmonary inflammation while exaggerating innate immune defenses by strongly influencing functions of inflammatory cells including dendritic cells, monocyte/macrophages, T cells, and B cells along with structural epithelial cells. This review dissects the effects of vitamin D on the inflammatory cells and their therapeutic relevance in pulmonary diseases. Although, the data obtained is very limited and needs further corroboration but presents an exciting area of further research. This is because of its ease of supplementation and development of personalized medicine which could lead us to an effective adjunct and cost-effective method of therapeutic modality for highly fatal pulmonary diseases.

Biological, nutritional, and therapeutic significance of Moringa oleifera Lam.

The genus Moringa Adans. comprises 13 species, of which Moringa oleifera Lam. native to India and cultivated across the world owing to its drought and frost resistance habit is widely used in traditional phytomedicine and as rich source of essential nutrients. Wide spectrum of phytochemical ingredients among leaf, flower, fruit, seed, seed oil, bark, and root depend on cultivar, season, and locality. The scientific studies provide insights on the use of M. oleifera with different aqueous, hydroalcoholic, alcoholic, and other organic solvent preparations of different parts for therapeutic activities, that is, antibiocidal, antitumor, antioxidant, anti-inflammatory, cardio-protective, hepato-protective, neuro-protective, tissue-protective, and other biological activities with a high degree of safety. A wide variety of alkaloid and sterol, polyphenols and phenolic acids, fatty acids, flavanoids and flavanol glycosides, glucosinolate and isothiocyanate, terpene, anthocyanins etc. are believed to be responsible for the pragmatic effects. Seeds are used with a view of low-cost biosorbent and coagulant agent for the removal of metals and microbial contamination from waste water. Thus, the present review explores the use of M. oleifera across disciplines for its prominent bioactive ingredients, nutraceutical, therapeutic uses and deals with agricultural, veterinarian, biosorbent, coagulation, biodiesel, and other industrial properties of this "Miracle Tree."

Antinociceptive properties of 25-methoxy hispidol A, a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF-κB signalling in mice.

The 25-methoxy hispidol A (25-MHA) is a triterpenoid, isolated from the immature fruit of Poncirus trifoliata (Rutaceae). The pretreatment with 25-MHA markedly (p < 0.001) attenuated the formalin-induced biphasic responses as well as acetic acid-induced writhing responses. The intraperitoneal administration of 25-MHA significantly attenuated the mechanical hyperalgesia (p < 0.001) and allodynia (p < 0.05). Similarly, 25-MHA also significantly attenuated (p < 0.001) complete Freund's adjuvant (CFA)-induced paw edema in mice. The 25-MHA treatment significantly attenuated the production of nuclear kappa B (NF-κB) (p65 nuclear subunit). The cytokines are the important mediators of inflammation and pain; however, treatment with 25-MHA exhibited significant inhibition (p < 0.001) on the mRNA expression levels of various inflammatory mediators. The 25-MHA administration also significantly enhanced antioxidant enzymes (p < 0.001) and inhibited the oxidative stress markers. The current study indicates that 25-MHA significantly (p < 0.001) inhibited the nitric oxide (NO) in mice plasma. Similarly, the haematoxylin and eosin (H&E) staining shows that 25-MHA administration significantly inhibited the inflammatory process in the mice paw tissue compared with the CFA-treated group. The 25-MHA treatment did not exhibited any toxicity on the liver, kidney, muscles strength, and motor co-ordination in mice. The 25-MHA was coadministered with the various drugs such as tramadol, piroxicam, and gabapentin to observe the synergistic effect.

Effect of 25-methoxy hispidol A isolated from Poncirus trifoliate against bacteria-induced anxiety and depression by targeting neuroinflammation, oxidative stress and apoptosis in mice.

Neuroinflammation, oxidative stress and apoptosis are implicated in the pathogenesis of neuropsychiatric diseases like anxiety and depression. 25-Methoxyhispidol A (25-MHA) is a triterpenoid isolated from the immature fruit of Poncirus trifoliate. Recently, its crude extracts have been shown to exhibit anti-bacterial and anti-inflammatory activities. The current study investigated the effect of 25-MHA (1, 5 and 10 mg/kg) against bacteria-induced anxiety and depression-like behaviors in mice. Mice were challenged intraperitoneally (i.p.) with LPS (0.83 mg/kg), S. aureus and E. coli after 30 min of 25-MHA treatment. 25-MHA (10 mg/kg) significantly mitigated the anxiety-like behavior as indicated by the results of elevated plus maze test, open field test, and light-dark box test. It also demonstrated the anti-depressant like effect by significantly reducing the immobility time in tail suspension test and forced swim test. The oxidative stress was reduced by pretreatment with 25-MHA, improving the antioxidant enzymes level such as glutathione, glutathione sulfo-transferase, and catalase. Similarly, 25-MHA attenuated the bacterial infection induced neuroinflammation by inhibiting the interleukin- 6 (IL-6), interleukin-1 beta (IL-1ß), and tumor necrosis factor-α (TNF-α) levels in prefrontal cortex and hippocampus regions. Pretreatment of 25-MHA also decreased the cortisol level and prevented changes in the thickness of the granular layer in the dentate gyrus. It also inhibited the DNA damage in hippocampus region as analyzed by comet assay. Hence, present results demonstrated that 25-MHA possesses anti-anxiety and anti-depressant activities due to the ability to reduce neuroinflammatory, oxidative stress and apoptosis induced by the administration of LPS, E. coli, and S. aureus.

Biogenic pentagonal silver nanoparticles for safer and more effective antibacterial therapeutics.

BACKGROUND: Biological synthesis of nanomaterials possesses unprecedented potential in the production of nanomaterials due to their ability to produce nanomaterials with improved biocompatibility in addition to eco-friendly synthetic procedures. METHODS: This article reports the isolation of an air-borne fungus from the campus of Integral University, Lucknow, with an exceptional ability to withstand very high concentrations of silver salt. The fungus was found to produce pentagonal silver nanoparticles (AgPgNps) when silver ions were reduced from silver nitrate. Molecular analysis and biochemical characterization techniques based on 18-seconds rRNA identified the fungus to belong to the Aspergillus sp. with the NCBI accession no KF913249. Material characterization techniques including ultraviolet (UV)-visible spectroscopy, transmission electron microscopy, and zeta potential analysis were used to satisfactorily characterize the as-synthesized AgPgNps. RESULTS: The AgPgNps synthesized by the fungus Aspergillus sp. exhibit an absorption that is maximum centered at about 416 nm, with a standard particle size of 23.22±2 nm. These AgPgNps exhibited broad-spectrum antimicrobial activities against an array of bacterial pathogens with remarkable minimum inhibitory concentration (MIC50) values: Staphylococcus aureus (ATCC 25923) - 9.230 µg/mL, Bacillus sp. (ATCC 14593) - 12.781 µg/mL, Escherichia coli (ATCC 25922) - 5.063 µg/mL, and Klebsiella pneumoniae (ATCC 13883) - 5.426 µg/mL. In vitro cytotoxicity analysis of biosynthesized AgPgNps showed a dose-response activity against human cervical cancer cell line (HeLa) and adenocarcinoma cells (A549) with MIC50 values of 0.038 µg/mL and 0.044 µg/mL, respectively. CONCLUSION: These findings are very crucial to evaluate the biosynthetic process for the synthesis of nanoparticles (NPs) with unique properties. These NPs may find potential applications in sensing, medicine, and antimicrobial and anticancer therapies.

Biaryl scaffold-focused virtual screening for anti-aggregatory and neuroprotective effects in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a primary cause of dementia in ageing population affecting more than 35 million people around the globe. It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (Aß) protein. Aß is formed by the cleavage of membrane embedded amyloid precursor protein (APP) by using enzyme 'transmembrane aspartyl protease, ß-secretase'. Inhibition of ß-secretase is a viable strategy to prevent neurotoxicity in AD. Another strategy in the treatment of AD is inhibition of acetylcholinesterase. This inhibition reduces the degradation of acetylcholine and temporarily restores the cholinergic function of neurons and improves cognitive function. Monoamine oxidase and higher glutamate levels are also found to be linked with Aß peptide related oxidative stress. Oxidative stress leads to reduced activity of glutamate synthase resulting in significantly higher level of glutamate in brain. The aim of this study is to perform in silico screening of a virtual library of biaryl scaffold containing compounds potentially used for the treatment of AD. Screening was done against the primary targets of AD therapeutics, acetylcholinesterase, ß-secretase (BACE1), Monoamine oxidases (MAO) and N-Methyl-D-aspartate (NMDA) receptor. Compounds were screened for their inhibitory potential by employing molecular docking approach using AutoDock vina. Binding energy scores were embodied in the heatmap to display varies strengths of interactions of the ligands targeting AD. RESULTS: Several ligands showed notable interaction with at least two targets, but the strong interaction with all the targets is shown by very few ligands. The pharmacokinetics of the interacting ligands was also predicted. The interacting ligands have good drug-likeness and brain availability essential for drugs with intracranial targets. CONCLUSION: These results suggest that biaryl scaffold may be pliable to drug development for neuroprotection in AD and that the synthesis of further analogues to optimize these properties should be considered.

Gold nanoconjugates reinforce the potency of conjugated cisplatin and doxorubicin.

Osteosarcoma or osteogenic sarcoma is the most common and prevalent cancerous tumor of bone and occurs especially in children and teens. Recent treatment strategy includes a combination of both chemotherapy and surgeries. Although, the use of single drug-based chemotherapy treatment remains unsatisfactory. Therefore, combinatorial therapy has emerged as a potential strategy for treatment with limited side- effects. Here, we evaluated the combinatorial anticancerous effect of cisplatin (CIS) and doxorubicin (DOX) bioconjugated bromelain encapsulated gold nanoparticles (B-AuNPs conjugated CIS and DOX) in the treatment of osteosarcoma. The synthesized B-AuNPs conjugated CIS and DOX were characterized by various characterization techniques like UV-vis spectroscopy, TEM, DLS and zeta potential to ensure the synthesis, size, shape, size distribution and stability. Drug loading efficiency bioconjugation of CIS and DOX was ensured by UV-vis spectroscopy. Bioconjugation of CIS and DOX was further confirmed using UV-vis spectroscopy, TEM, DLS, Zeta potential and FT-IR analysis. The combinatorial effect of CIS and DOX in B-AuNPs conjugated CIS and DOX showed highly improved potency against MG-63 and Saos-2 cells at a very low concentration where primary osteoblasts didn't show any cytotoxic effect. The apoptotic effect of B-AuNPs conjugated CIS and DOX on osteosarcoma and primary osteoblasts cells were analyzed by increased permeability of the cell membrane, condensed chromatin and deep blue fluorescent condensed nucleus. The results clearly showed that B-AuNPs conjugated CIS and DOX significantly improved the potency of both the chemotherapeutic drugs by delivering them specifically into the nucleus of cancer cells through caveolae-dependent endocytosis. Thus, the greater inhibitory effect of combinatorial drugs (B-AuNPs conjugated CIS and DOX) over single drug based chemotherapy would be of great advantage during osteosarcoma treatment.

Magnetic Nanoparticles: Properties, Synthesis and Biomedical Applications.

Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine.

Bacteria Etiological Agents Causing Lower Respiratory Tract Infections and Their Resistance Patterns.

BACKGROUND: Lower respiratory tract infections (LTRIs) are among the most common infectious diseases with potential life-threatening complications. METHODS: The study consisted of 426 patients with suspected LTRIs from mid and far western region of Nepal between September 2011 and July 2014. The specimens were collected and processed according to the standard microbiological methods at the Central Laboratory of Microbiology of Nepalgunj Medical College, Nepal. RESULTS: Among the isolated Gram-positive organisms, Streptococcus pneumonia (n = 30, 51.7%) was the most predominant pathogen, followed by Staphylococcus aureus (n = 28, 48.3%). Among the isolated Gram-negative organisms, Pseudomonas aeruginosa (n = 71, 35.32%) was the most predominant pathogen, followed by Haemophilus influenzae (n = 68, 33.83%), Klebsiella pneumonia (n = 36, 17.19%), and Escherichia coli (n = 26, 12.94%). The pattern of resistance varied regarding the bacteria species, and there were multi-resistant isolates. Also, a significant difference (P value less than 0.05) was observed between males and females for each type of bacterial species. Among 259 isolates, 86 (33.20%) were from children aged 1-10 years, which were statistically significant (P valuse less than 0.05) compared to the other age groups. CONCLUSIONS: P. aeruginosa and H. influenzae (Gram-negative) and S. pnemoniae (Gram-positive) were the most common bacterial isolates recovered from LTRIs. Age group of 1-10 years old was at a higher risk. Many isolates showed appreciable levels of antibiotic resistance due to antibiotic abuse. There is a need to increase surveillance and develop better strategies to curb the increasing prevalence of LRTI in this region of Nepal.