Phytochemical Analysis and Antimicrobial Potential of Parthenium hysterophorous and Lantana camara.

BACKGROUND: Parthenium hysterophorous and Lantana camara are notable for their significant phytochemical and antimicrobial properties. Advancements in phytochemical research have led to the development of novel formulations and products derived from P. hysterophorus and L. camara. For instance, patent extracts from these plants have been utilized in the formulation of pharmaceutical drugs, herbal supplements, cosmeceuticals, and agricultural products. P. hysterophorous, commonly known as Santa Maria feverfew or Congress grass, contains various bioactive compounds like terpenoids, flavonoids, phenolics, and alkaloids.These compounds are the key to its medicinal properties, particularly its antimicrobial activity. On the other hand, L. camara, often referred to as wild sage, is rich in phytochemicals such as terpenoids, flavonoids, and alkaloid glycosides. METHODS: P. hysterophorous and L. camara plants selected and checking their antimicrobial activity by agar well diffusion method. RESULTS: In our study, we found that the leaf extract of P. hysterophorous exhibited the most potent antibacterial activity against E. coli. P. hysterophorous exhibited the most potent antifungal activity against A. niger and T. viride, with a diameter of inhibition zone measuring 12 mm, followed by A. flavus and A. parasiticus. In case of L. camara, the inhibitory zone ranging from 14 to 18 mm was detected against S. abony, P. aeruginosa, E. coli, and K. pneumonia. The leaf extract of the maximum zone of inhibition in case of L. camara was shown by A. flavus (12mm). CONCLUSION: The present study suggests that these two weeds could be useful in the development of bactericides and fungicides.

Unleashing the role of e-word of mouth on purchase intention in select Facebook fan pages of smart phone users.

OBJECTIVE: This study aims to examine the impact of e-WOM on customer purchase intentions in Facebook fan pages using theories of trust, value co-creation and brand attitude. The present research has set out to explore this emerging domain of study and has thus developed & tested propositions which attempt to establish a relationship between e-WOM and customer's purchase intentions. A deeper understanding of this possible association is obtained by studying the mediating roles of Trust, Value Co-Creation, Brand Image and Brand Attitude. METHODOLOGY: The context for exploring this phenomenon is chosen to be the fan pages of smartphone brands on Facebook. The study involved conducting a sample survey of 490 respondents, comprising of both male and female, who belong to 5 smartphone brands Facebook fan pages-Samsung, Moto G, Lenovo, MI and ASUS are considered for the study. Out of which sample of 100 each has been targeted individually. FINDINGS: The findings suggested that e-WOM significantly predicts the purchase intentions of the customers of a specific product and considerable impacted on the purchase decision. The findings of the study also reveal that customer 's trust beliefs, perceived value co-creation, brand image and brand attitude partially mediate in between relationships of e-WOM and purchase intention. CONCLUSION: The actual presence of different types of consumer electronics brands on the social media, more prominently, the smartphones, which undoubtedly are the most ubiquitous product of this segment. In fact, this indicates that presence on social media is a well- thought organizational strategy developed by companies to gain partial control over the customer 's decision- making process by establishing a close connect with the customers for a long period. IMPLICATION: This consequence will significantly impact the decision-making process of marketers or practitioners in relation to their marketing tactics. This research also indicates that marketers could devise more effective methods for distributing marketing content through social networking sites, while corporations can cultivate favorable electronic word-of-mouth for their products or services. Through the implementation of social media marketing strategies, companies can increase their sales volume and generate higher revenue. The study examined the role of trust, virtual community participation, and desire to purchase as mediators on smartphone brand fan sites on Facebook. It was observed that these factors had a partial influence on customer purchase intention.

Initiation of Haploidentical Stem Cell Transplantation With Post-Transplant Cyclophosphamide in Children: A Low-Middle-Income Country Institutional Experience.

BACKGROUND: Haploidentical hematopoietic stem cell transplant (HSCT) is a curative treatment especially for countries where bone marrow registries are nonexistent. We present our experience with haploidentical HSCT in pediatric patients. METHODS: Retrospective data collected and analyzed for patients ≤18 years, from January 2017 to December 2022. RESULTS: The cohort consisted of 20 patients with median age at transplant of 61.5 (IQR: 124) months. Fourteen (70%) were malignant and 6 (30%) were benign diseases. Donors were father in majority (9/20; 45%). Stem cell source was peripheral blood 8, marrow 8, and combined 4. c-specific antibodies were positive in 6 (30%). Median CD34 cell dose infused: 9.35 × 106/kg. Median engraftment time: 15 (IQR: 17) days. Acute and chronic graft-versus-host disease (GVHD) occurred in 12/20 (60%) and 5/20 (25%), respectively. Complications included infection/sepsis (14/20; 70%), cytomegalovirus reactivation (14/20; 70%), sinusoidal obstruction syndrome (1/20; 5%), primary graft failure (PGF) (6/20; 30%), and secondary graft failure (4/20; 20%). PGF was more common in benign conditions (p = 0.003) and less prevalent in cases with aGVHD (p = 0.007). aGVHD was more common in malignant conditions (p = 0.007). Overall survival (OS), relapse-free survival (RFS), and treatment-related mortality (TRM) were 40%, 50%, and 35%, respectively. Median time of survival and relapse were 8 (IQR: 15) and 9 (IQR: 13) months, respectively. CONCLUSION: OS was comparable to that of other low-middle-income countries. GVHD was a major challenge, along with sepsis and CMV infection. Half of the leukemias relapsed. Graft failure was a major concern in nonmalignant diseases.

Elucidating the Immune Response to SARS-CoV-2: Natural Infection versus Covaxin/Covishield Vaccination in a South Indian Population.

A natural infection or a vaccination can initially prime the immune system to form immunological memory. The immunity engendered by vaccination against COVID-19 versus natural infection with SARS-CoV-2 has not been well studied in the Indian population. In this study, we compared the immunity conferred by COVID-19 vaccines to naturally acquired immunity to SARS-CoV-2 in a South Indian population. We examined binding and neutralizing antibody (NAb) levels against the ancestral and variant lineages and assessed the ex vivo cellular parameters of memory T cells, memory B cells, and monocytes and finally measured the circulating cytokine response. COVID-19 vaccination stimulates heightened levels of IgG antibodies against the original strain of SARS-CoV-2, as well as increased binding to the spike protein and neutralizing antibody levels. This enhanced response extends to variant lineages such as B.1.617.2 (Delta, India), B.1.1.529 (Omicron, India), B.1.351 (Beta, South Africa), and B.1.1.7 (Alpha, UK). COVID-19 vaccination differs from SARS-CoV-2 infection by having increased frequencies of classical memory B cells, activated memory B and plasma cells, CD4/CD8 T cells of effector memory, effector cells, stem cell-like memory T cells, and classical and intermediate monocytes and diminished frequencies of CD4/CD8 T cells of central memory and non-classical monocytes in vaccinated individuals in comparison to those with natural infection. Thus, COVID-19 vaccination is characterized by enhanced humoral responses and robust activation of innate and memory T cell responses in comparison to natural infection in a South Indian population.

Quantifying Plant Signaling Pathways by Integrating Luminescence-Based Biosensors and Mathematical Modeling.

Plants have evolved intricate signaling pathways, which operate as networks governed by feedback to deal with stressors. Nevertheless, the sophisticated molecular mechanisms underlying these routes still need to be comprehended, and experimental validation poses significant challenges and expenses. Consequently, computational hypothesis evaluation gains prominence in understanding plant signaling dynamics. Biosensors are genetically modified to emit light when exposed to a particular hormone, such as abscisic acid (ABA), enabling quantification. We developed computational models to simulate the relationship between ABA concentrations and bioluminescent sensors utilizing the Hill equation and ordinary differential equations (ODEs), aiding better hypothesis development regarding plant signaling. Based on simulation results, the luminescence intensity was recorded for a concentration of 47.646 RLUs for 1.5 µmol, given the specified parameters and model assumptions. This method enhances our understanding of plant signaling pathways at the cellular level, offering significant benefits to the scientific community in a cost-effective manner. The alignment of these computational predictions with experimental results emphasizes the robustness of our approach, providing a cost-effective means to validate mathematical models empirically. The research intended to correlate the bioluminescence of biosensors with plant signaling and its mathematical models for quantified detection of specific plant hormone ABA.

Effects of access condition on substance use disorder-like phenotypes in male and female rats self-administering MDPV or cocaine.

Substance use disorder (SUD) is a heterogeneous disorder, where severity, symptoms, and patterns of use vary across individuals. Yet, when rats self-administer cocaine under short-access conditions, their behavior tends to be well-regulated, though individual differences can emerge with long- or intermittent-access. In contrast, significant individual differences emerge when rats self-administer 3,4-methylenedioxypyrovalerone (MDPV), even under short-access conditions, wherein ~30 % of rats exhibit high levels of drug-taking. This study assessed SUD-like phenotypes of male and female rats self-administering MDPV or cocaine by comparing level of drug intake, responding during periods of signaled drug unavailability, and sensitivity to footshock punishment to determine whether: (1) under short-access conditions, rats that self-administer MDPV will exhibit a more robust SUD-like phenotype than rats that self-administer cocaine; (2) female rats will have a more severe phenotype than male rats; and (3) compared to short-access, long- and intermittent-access to MDPV or cocaine self-administration will result in a more robust SUD-like phenotype. Compared to cocaine, rats that self-administered MDPV exhibited a more severe phenotype, even under short-access conditions. Long- and intermittent-access to cocaine and MDPV temporarily altered drug-taking patterns but did not systematically change SUD-like phenotypes. Behavioral and quantitative autoradiography studies suggest phenotypic differences are not due to expression of dopamine transporter, dopamine D2 or D3 receptors, or 5-HT1B, 5-HT2A, or 5-HT2C receptors. This study suggests individuals who use synthetic cathinones may be at greater risk for developing a SUD, and short-access MDPV self-administration may provide a useful method to study the transition to disordered substance use in humans.

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib).

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats. The results of the study revealed that pimitespib effectively suppressed hepatic inflammation and fibrogenesis by modulating HSP90's control over the NFκB/NLRP3/caspase-1 axis. In vitro experiments demonstrated that pimitespib reduced LDH levels and increased hepatocyte survival, whereas in vivo, it prolonged the survival of rats with hepatic fibrosis. Additionally, pimitespib exhibited improvements in the function and microscopic characteristics of rat livers. Pimitespib effectively inhibited NFκB, which serves as the priming signal for NLRP3 activation. Pimitespib's inhibitory effect on NLRP3, identified as an HSP90 client protein, plays a central role in the observed anti-fibrotic effect. The simultaneous inhibition of both priming and activation signals of NLRP3 by pimitespib led to a reduction in caspase-1 activity and subsequent suppression of the N-terminal fragment of gasdermin D, ultimately constraining hepatocyte pyroptotic cell death. These diverse effects were associated with a decrease in the transcription of inflammatory mediators IL-1ß, IL-18, and TNF-α, as well as the fibrogenic mediators TGF-ß, TIMP-1, PDGF-BB, and Col1a1. Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy.

Modified frankincense resin stabilized gold nanoparticles for enhanced antioxidant and synergetic activity in in-vitro anticancer studies.

For the first time, Frankincense resin (FR) has been carboxymethylated to produce CMFR - AuNPs and the conjugate was utilized for the Doxorubicin drug loading. The carboxymethylation of the carboxylic, phenolic, and hydroxyl functional groups of FR has been developed into carboxymethylated Frankincense resin (CMFR). A novel CMFR-AuNPs was synthesized using the developed CMFR as a stabilizing and reducing agent. The antibacterial, antioxidant, and in-vitro anticancer activities were investigated by using CMFR-AuNPs and CMFR - AuNPs@DOX. CMFR-AuNPs demonstrated antioxidative properties by quenching DPPH radicals effectively. CMFR-AuNPs and DOX@CMFR-AuNPs demonstrated strong antibacterial activity against K. pneumoniae, S. aureus, B. subtilis, and E. coli. The cell viability was tested for CMFR -AuNPs at various concentrations of Dox-loaded CMFR -AuNPs (CMFR-AuNPs + Dox1, CMFR-AuNPs + Dox 2, & CMFR-AuNPs + Dox 3). The highest inhibition was observed on MCF-7 and HeLa cell lines using CMFR-AuNPs + Dox 3, respectively. Various techniques such as UV, FTIR, TGA, XRD, SEM, EDAX and TEM were used to characterize the designed CMFR and CMFR-AuNPs. After carboxy methylation, the amorphous nature of FR changed to crystallinity, as reflected in the XRD spectra. The XRD spectrum of the CMFR- AuNPs showed FCC structure due to the involvement of hydroxyl and carboxylic functional groups of CMFR strongly bound with the AuNPs. TGA results revealed that the CMFR is thermally more stable than FR. TEM revealed that CMFR - AuNPs were well dispersed, spherical, and hexagonal with an average diameter of 7 to 10 nm, while the size of doxorubicin loaded (DOX@CMFR-AuNPs) AuNPs was 11 to 13 nm. Green CMFR-AuNPs have the potential to enhance the drug loading and anticancer efficacy of drugs.

S-glutathionylation in hepatocytes is involved in arsenic-induced liver fibrosis through activation of the NLRP3 inflammasome, an effect alleviated by NAC.

Arsenic, a toxicant widely distributed in the environment, is considered as a risk factor for liver fibrosis. At present, the underlying mechanism still needs to be explored. In the present study, we found that, for mice, chronic exposure to arsenic induced liver fibrosis, activated the NLRP3 inflammasome, and increased the levels of reactive oxygen species (ROS). After hepatocytes were co-cultured with hepatic stellate cells (HSCs), we observed the arsenic-activated NLRP3 inflammasome in hepatocytes, and the co-cultured HSCs were activated. Further, we found that, in livers of mice, arsenic disturbed GSH metabolism and promoted protein S-glutathionylation. A 3D molecular docking simulation suggested that NLRP3 binds with GSH, which was confirmed by immunoprecipitation experiments. N-acetylcysteine (NAC) increased the levels of GSH in hepatocytes, which suppressed the S-glutathionylation of NLRP3 and blocked arsenic-induced activation of the NLRP3 inflammasome. Mechanistically, an imbalance of the redox state induced by arsenic promotes the S-glutathionylation of NLRP3, which regulates activation of the NLRP3 inflammasome, leading into the activation of HSCs. Moreover, NAC increases the levels of GSH to block arsenic-induced S-glutathionylation of NLRP3, thereby blocking arsenic-induced liver fibrosis. Thus, via activating HSCs, the S-glutathionylation of NLRP3 in hepatocytes is involved in arsenic-induced liver fibrosis, and, for hepatocytes, NAC alleviates these effects by increasing the levels of GSH. These results reveal a new mechanism and provide a possible therapeutic target for the liver fibrosis induced by environmental factors.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study.

BACKGROUND: The wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated. METHODS: In the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed. RESULTS: The HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure. CONCLUSIONS: This study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Secondary metabolite profile of Streptomyces spp. changes when grown with the sub-lethal concentration of silver nanoparticles: possible implication in novel compound discovery.

The decline of new antibiotics and the emergence of multidrug resistance in pathogens necessitates a revisit of strategies used for lead compound discovery. This study proposes to induce the production of bioactive compounds with sub-lethal concentrations of silver nanoparticles (Ag-NPs). A total of Forty-two Actinobacteria isolates from four Saudi soil samples were grown with and without sub-lethal concentration of Ag-NPs (50 µg ml-1). The spent broth grown with Ag-NPs, or without Ag-NPs were screened for antimicrobial activity against four bacteria. Interestingly, out of 42 strains, broths of three strains grown with sub-lethal concentration of Ag-NPs exhibit antimicrobial activity against Staphylococcus aureus and Micrococcus luteus. Among these, two strains S4-4 and S4-21 identified as Streptomyces labedae and Streptomyces tirandamycinicus based on 16S rRNA gene sequence were selected for detailed study. The change in the secondary metabolites profile in the presence of Ag-NPs was evaluated using GC-MS and LC-MS analyses. Butanol extracts of spent broth grown with Ag-NPs exhibit strong antimicrobial activity against M. luteus and S. aureus. While the extracts of the controls with the same concentration of Ag-NPs do not show any activity. GC-analysis revealed a clear change in the secondary metabolite profile when grown with Ag-NPs. Similarly, the LC-MS patterns also differ significantly. Results of this study, strongly suggest that sub-lethal concentrations of Ag-NPs influence the production of secondary metabolites by Streptomyces. Besides, LC-MS results identified possible secondary metabolites, associated with oxidative stress and antimicrobial activities. This strategy can be used to possibly induce cryptic biosynthetic gene clusters for the discovery of new lead compounds.

Mitigating drought-induced oxidative stress in wheat (Triticum aestivum L.) through foliar application of sulfhydryl thiourea.

Drought stress is a major abiotic stress affecting the performance of wheat (Triticum aestivum L.). The current study evaluated the effects of drought on wheat phenology, physiology, and biochemistry; and assessed the effectiveness of foliar-applied sulfhydryl thiourea to mitigate drought-induced oxidative stress. The treatments were: wheat varieties; V1 = Punjab-2011, V2 = Galaxy-2013, V3 = Ujala-2016, and V4 = Anaaj-2017, drought stress; D1 = control (80% field capacity [FC]) and D2 = drought stress (40% FC), at  the reproductive stage, and sulfhydryl thiourea (S) applications; S0 = control-no thiourea and S1 = foliar thiourea application @ 500 mg L-1. Results of this study indicated that growth parameters, including height, dry weight, leaf area index (LAI), leaf area duration (LAD), crop growth rate (CGR), net assimilation rate (NAR) were decreased under drought stress-40% FC, as compared to control-80% FC. Drought stress reduced the photosynthetic efficiency, water potential, transpiration rates, stomatal conductances, and relative water contents by 18, 17, 26, 29, and 55% in wheat varieties as compared to control. In addition, foliar chlorophyll a, and b contents were also lowered under drought stress in all wheat varieties due to an increase in malondialdehyde and electrolyte leakage. Interestingly, thiourea applications restored wheat growth and yield attributes by improving the production and activities of proline, antioxidants, and osmolytes under normal and drought stress as compared to control. Thiourea applications improved the osmolyte defense in wheat varieties as peroxidase, superoxide dismutase, catalase, proline, glycine betaine, and total phenolic were increased by 13, 20, 12, 17, 23, and 52%; while reducing the electrolyte leakage and malondialdehyde content by 49 and 32% as compared to control. Among the wheat varieties, Anaaj-2017 showed better resilience towards drought stress and also gave better response towards thiourea application based on morpho-physiological, biochemical, and yield attributes as compared to Punjab-2011, Galaxy-2013, and Ujala-2016. Eta-square values showed that thiourea applications, drought stress, and wheat varieties were key contributors to most of the parameters measured. In conclusion, the sulfhydryl thiourea applications improved the morpho-physiology, biochemical, and yield attributes of wheat varieties, thereby mitigating the adverse effects of drought.  Moving forward, detailed studies pertaining to the molecular and genetic mechanisms under sulfhydryl thiourea-induced drought stress tolerance are warranted.

Formulation, Optimization, and Evaluation of Non-Propellent Foam-Based Formulation for Burn Wounds Treatment.

Burn injuries worldwide pose significant health risks due to frequent microbial infections, which worsen complications and increase mortality rates. The conventional antimicrobial formulations are available in the form of ointments and creams. These formulations are very greasy and stick to the clothes. The applications of these formulations by finger or applicator produce pain in the affected area and incur the possibility of microbial infection. To overcome these hurdles, authors developed a novel non-propellent foam (NPF) based formulation containing chlorhexidine for effective topical delivery. Initially, NPF containing Labrasol® (26.7%), sodium lauryl sulfate (1.2%), hydroxy propyl methyl cellulose (0.56%), butylated hydroxytoluene (0.1%), ethanol (1%), and distilled water was prepared and assessed for its consistency, and ability to form foam. The NPF was statistically optimized using the Box-Behnken design to determine the effect of polymer and surfactants on the critical foam properties. The optimized formulation showed a collapse time of 45 s with a unique nature of collapsing upon slight touch which is highly beneficial for burn patients with microbial infection. The diffusion study showed that more than 90% of the drug was released within 6 h. The skin permeation study showed that 23% of the total drug permeated through the skin after 6 h with 7.64 µg/cm2/h permeation flux. The developed formulation showed good antibacterial activity. The minimum inhibitory concentration of prepared NPF was found to be 2.5 µg/mL, 2.5 µg/mL, and 5.0 µg/mL against E. coli (MTCC-1687), P. aeruginosa (MTCC-1688), and S aureus (MTCC-737) respectively. The developed NPF formulation showed quick collapse time, excellent spreadability, good anti-bacterial activity, and a non-sticky nature representing a promising avenue for burn wound treatment without using any applicator.

Cellulose ether and carbopol 971 based gastroretentive controlled release formulation design, optimization and physiologically based pharmacokinetic modeling of ondansetron hydrochloride minitablets.

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (Fpred) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of Fpred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of Fpred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents.

Construction of an adverse outcome pathway framework for arsenic-induced lung cancer using a network-based approach.

Environmental pollutants are considered as a cause of tumorigenesis, but approaches to assess their risk of causing tumors remain insufficient. As an alternative approach, the adverse outcome pathway (AOP) framework is used to assess the risk of tumors caused by environmental pollutants. Arsenic is a pollutant associated with lung cancer, but early assessment of lung cancer risk is lacking. Therefore, we applied the AOP framework to arsenic-induced lung cancer. A systematic review revealed increased risks of lung cancer following exposure to a range of arsenic concentrations in drinking water (OR = 1.83, 95 % CI = 1.46-2.30). We obtained, from public databases, genes related to risk of arsenic-induced lung cancer. Then, Cox and LASSO regressions were used to screen target genes from the risk genes. Subsequently, target genes, phenotypes, and pathways were used to construct the computational AOP network, which was determined by Cytoscape to have 156 edges and 45 nodes. Further, target genes, phenotypes, and pathways were used as molecular initiating events and key events to construct the AOP framework depending on upstream and downstream relationships. In the AOP framework, by Weight of Evidence, arsenic exposure increased levels of EGFR, activated the PI3K/AKT pathway, regulated cell proliferation by promoting the G1/S phase transition, and caused generation of lung cancers. External validation was achieved through arsenite-induced, malignant transformed human bronchial epithelial (HBE) cells. Overall, these results, by integration into existing data to construct an AOP framework, provide insights into the assessment of lung cancer risk for arsenic exposure. Special attention needs to be focused on populations with low-dose arsenic exposure.

Targeting of S-phase kinase associated protein 2 stabilized tumor suppressors leading to apoptotic cell death in squamous skin cancer cells.

S-phase kinase-associated protein 2 (Skp2) is an F-box protein overexpressed in human cancers and linked with poor prognosis. It triggers cancer pathogenesis, including stemness and drug resistance. In this study, we have explored the potential role of Skp2 targeting in restoring the expression of tumor suppressors in human cutaneous squamous cell carcinoma (cSCC) cells. Our results showed that genetic and pharmacological Skp2 targeting markedly suppressed cSCC cell proliferation, colony growth, spheroid formation, and enhanced sensitization to chemotherapeutic drugs. Further, western blot results demonstrated restoration of tumor suppressor (KLF4) and CDKI (p21) and suppression of vimentin and survivin in Skp2-knocked-down cSCC cells. Importantly, we also explored that Skp2 targeting potentiates apoptosis of cSCC cells through MAPK signaling. Moreover, co-targeting of Skp2 and PI3K/AKT resulted in increased cancer cell death. Interestingly, curcumin, a well-known naturally derived anticancer agent, also inhibits Skp2 expression with concomitant CDKI upregulation. In line, curcumin suppressed cSCC cell growth through ROS-mediated apoptosis, while the use of N-acetyl cysteine (NAC) reversed curcumin-induced cell death. Curcumin treatment also sensitized cSCC cells to conventional anticancer drugs, such as cisplatin and doxorubicin. Altogether, these data suggest that Skp2 targeting restores the functioning of tumor suppressors, inhibits the expression of genes associated with cell proliferation and stemness, and sensitizes cancer cells to anticancer drugs. Thus, genetic, and pharmacological ablation of Skp2 can be an important strategy for attenuating cancer pathogenesis and associated complications in skin squamous cell carcinoma.

Urdu translation, cross-cultural validation and reliability of ECOS-16 questionnaire among post-menopausal women with osteopenia.

BACKGROUND: Escala de Calidad de vida Osteoporosis (ECOS-16) was originally developed in Spanish to evaluate the quality of life (QoL) in post-menopausal women (PMW) with osteoporosis or osteopenia based on the osteoporosis-specific QoL instruments. ECOS-16 has been translated into several languages, but the Urdu version is not yet available. OBJECTIVE: To translate the ECOS-16 Questionnaire into Urdu and determine its validity and reliability in PMW with osteopenia. METHODS: This was a linguistic validity and reliability study. ECOS-16 was translated into Urdu using Beaton's guidelines. Content validity was examined using Waltz's four-point ordinal scale. Twenty osteopenia-afflicted PMW aged 48-70 underwent pilot testing for face validity. Discriminant validity was determined by an independent T-test between PMW women with and without osteopenia. Convergent validity was assessed using Spearman's correlation coefficient. Cronbach's alpha and Intraclass correlation coefficient (ICC2,1) assessed internal consistency and test-retest reliability. The factor analysis was used to describe the factors. RESULTS: Each question's content validity ratio (CVR) was 0.83-1.00, while the scale's S-CVR was 0.96. Each question's Likert scale content validity index (CVI) was 0.91-0.93, while the scale's S-CVI was 0.91. Significant discriminant validity was found between groups in weeks I and II (p-value < 0.001). A correlation coefficient of 0.89 and 0.96 (p-value < 0.001) between Urdu ECOS-16 total score and SF-36 and EQ-5D scores suggests convergent validity. One component explained 83.86% of Urdu ECOS-16's variance in factor analysis. Excellent test-retest reliability (ICC2,1 = 0.990, 95% CI, 0.985-0.994, p-value < 0.001). Cronbach's alpha for standardized items was 0.995. CONCLUSION: ECOS-16 translated in Urdu is a valid and reliable questionnaire to assess QoL in PMW with osteopenia. It has a simple and easy language that can be understood easily by the Urdu-speaking population.

Genome wide nucleosome landscape shapes 3D chromatin organization.

The hierarchical chromatin organization begins with formation of nucleosomes, which fold into chromatin domains punctuated by boundaries and ultimately chromosomes. In a hierarchal organization, lower levels shape higher levels. However, the dependence of higher-order 3D chromatin organization on the nucleosome-level organization has not been studied in cells. We investigated the relationship between nucleosome-level organization and higher-order chromatin organization by perturbing nucleosomes across the genome by deleting Imitation SWItch (ISWI) and Chromodomain Helicase DNA-binding (CHD1) chromatin remodeling factors in budding yeast. We find that changes in nucleosome-level properties are accompanied by changes in 3D chromatin organization. Short-range chromatin contacts up to a few kilo-base pairs decrease, chromatin domains weaken, and boundary strength decreases. Boundary strength scales with accessibility and moderately with width of nucleosome-depleted region. Change in nucleosome positioning seems to alter the stiffness of chromatin, which can affect formation of chromatin contacts. Our results suggest a biomechanical "bottom-up" mechanism by which nucleosome distribution across genome shapes 3D chromatin organization.

Antibacterial Silver Nanoparticle Containing Polydopamine Hydrogels That Enhance Re-Epithelization.

A polydopamine polyelectrolyte hydrogel was developed by ionic crosslinking dextran sulfate with a copolymer of polyethyleneimine and polydopamine. Gelation was promoted by the slow hydrolysis of glucono-δ-lactone. Within this hydrogel, silver nanoparticles were generated in situ, ranging from 25 nm to 200 nm in size. The antibacterial activity of the hydrogel was proportional to the quantity of silver nanoparticles produced, increasing as the nanoparticle count rose. The hydrogels demonstrated broad-spectrum antibacterial efficacy at concentrations up to 108 cells/mL for P. aeruginosa, K. pneumoniae, E. coli and S. aureus, the four most prevalent bacterial pathogens in chronic septic wounds. In ex vivo studies on human skin, biocompatibility was enhanced by the presence of polydopamine. Dextran sulfate is a known irritant, but formulations with polydopamine showed improved cell viability and reduced levels of the inflammatory biomarkers IL-8 and IL-1α. Silver nanoparticles can inhibit cell migration, but an ex vivo human skin study showed significant re-epithelialization in wounds treated with hydrogels containing silver nanoparticles.

Preparation and functional characterization of pullulan-sodium alginate composite film enhanced with ultrasound-assisted clove essential oil Nanoemulsions for effective preservation of cherries and mushrooms.

Clove essential oil (CEO) exhibited potent antibacterial efficacy and are obtained from Eugenia caryophyllata tree flower buds. Herein, CEO nanoemulsions were prepared using various concentrations of casein protein treated with ultrasound for different time interval. The study demonstrated that CEO nanoemulsions with 5% casein protein subjected to ultrasound for 10 min displayed the most minimal particle size. The pullulan­sodium alginate film incorporated with nanoemulsions treated with ultrasound exhibited enhanced physico-mechanical characteristics. Based on the structural analysis, the application of ultrasonic treatment improved intermolecular compatibility and organized molecular structure by strengthening hydrogen bonds. Furthermore, the composite film displayed remarkable efficacy against E. coli and S. aureus as well as longer retention of essential oils. The use of the developed films to protect cherry fruits and mushrooms produced promising results, emphasizing their potential in food packaging applications.