Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20.

BACKGROUND: The repurposing of FDA-approved drugs for anti-cancer therapies is appealing due to their established safety profiles and pharmacokinetic properties and can be quickly moved into clinical trials. Cancer progression and resistance to conventional chemotherapy remain the key hurdles in improving the clinical management of colon cancer patients and associated mortality. METHODS: High-throughput screening (HTS) was performed using an annotated library of 1,600 FDA-approved drugs to identify drugs with strong anti-CRC properties. The candidate drug exhibiting most promising inhibitory effects in in-vitro studies was tested for its efficacy using in-vivo models of CRC progression and chemoresistance and patient derived organoids (PTDOs). RESULTS: Albendazole, an anti-helminth drug, demonstrated the strongest inhibitory effects on the tumorigenic potentials of CRC cells, xenograft tumor growth and organoids from mice. Also, albendazole sensitized the chemoresistant CRC cells to 5-fluorouracil (5-FU) and oxaliplatin suggesting potential to treat chemoresistant CRC. Mechanistically, Albendazole treatment modulated the expression of RNF20, to promote apoptosis in CRC cells by delaying the G2/M phase and suppressing anti-apoptotic-Bcl2 family transcription. CONCLUSIONS: Albendazole, an FDA approved drug, carries strong therapeutic potential to treat colon cancers which are aggressive and potentially resistant to conventional chemotherapeutic agents. Our findings also lay the groundwork for further clinical testing.

IL-22 regulates MASTL expression in intestinal epithelial cells.

Microtubule-associated serine-threonine kinase-like (MASTL) has recently been identified as an oncogenic kinase given its overexpression in numerous cancers. Our group has shown that MASTL expression is upregulated in mouse models of sporadic colorectal cancer and colitis-associated cancer (CAC). CAC is one of the most severe complications of chronic inflammatory bowel disease (IBD), but a limited understanding of the mechanisms governing the switch from normal healing to neoplasia in IBD underscores the need for increased research in this area. However, MASTL levels in patients with IBD and its molecular regulation in IBD and CAC have not been studied. This study reveals that MASTL is upregulated by the cytokine interleukin (IL)-22, which promotes proliferation and has important functions in colitis recovery; however, IL-22 can also promote tumorigenesis when chronically elevated. Upon reviewing the publicly available data, we found significantly elevated MASTL and IL-22 levels in the biopsies from patients with late-stage ulcerative colitis compared with controls, and that MASTL upregulation was associated with high IL-22 expression. Our subsequent in vitro studies found that IL-22 increases MASTL expression in intestinal epithelial cell lines, which facilitates IL-22-mediated cell proliferation and downstream survival signaling. Inhibition of AKT activation abrogated IL-22-induced MASTL upregulation. We further found an increased association of carbonic anhydrase IX (CAIX) with MASTL in IL-22-treated cells, which stabilized MASTL expression. Inhibition of CAIX prevented IL-22-induced MASTL expression and cell survival. Overall, we show that IL-22/AKT signaling increases MASTL expression to promote cell survival and proliferation. Furthermore, CAIX associates with and stabilizes MASTL in response to IL-22 stimulation.NEW & NOTEWORTHY MASTL is upregulated in colorectal cancer; however, its role in colitis and colitis-associated cancer is poorly understood. This study is the first to draw a link between MASTL and IL-22, a proinflammatory/intestinal epithelial recovery-promoting cytokine that is also implicated in colon tumorigenesis. We propose that IL-22 increases MASTL protein stability by promoting its association with CAIX potentially via AKT signaling to promote cell survival and proliferation.

Functionalization of ampicillin and gentamicin with biogenic copper nanoparticles (CuNPs) remodel antimicrobial and cytotoxic outcome against MDR clinical isolates.

The present study reports the functionalization of antibiotic-conjugated Alternanthera pungens and Trichodesma indicum copper nanoparticles (CuNPs). Initially, antibiotic profiling of multi-drug resistant (MDR) clinical isolates against five antibiotics was verified and then gentamicin and ampicillin conjugates of CuNPs were prepared. Biosynthesized nanostructures were characterized through UV-visible spectroscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction and scanning electron microscope. Biogenic synthesized CuNPs displayed highest antibacterial activity (24.0-31.3 mm inhibition zones) when capped with gentamicin as compared to the ampicillin-conjugated NPs which showed resistance against most of the bacterial species. A. pungens-derived conjugates of gentamicin (CuAp-GNT) along with the vehicle revealed 4.86 ± 0.20% and 4.25 ± 2.96% hemolytic potential and highest MDA production in S. typhimurium (3.18 ± 1.52 µg/mL and 6.31 ± 3.49 µg/mL) and K. pneumoniae (2.99 ± 0.90 µg/mL and 4.06 ± 1.20 µg/mL). Similarly, CuAp-GNT also showed highest DNA protection ability by displaying 1342.99 ± 11.87 band intensity. All-inclusive, CuAp showed more promising effects when conjugated with gentamicin indicating that capping of gentamicin with the active components of the plant-based copper nanostructures increases the antibacterial capacity of the drug. Hence, conjugation of antibiotics with bio-based sources offers great potential for identifying potent drug leads.

Discovery, synthesis and biological evaluation of a series of N-(phenylcarbamothioyl)-2-napthamides as inhibitors of Claudin-1.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, despite advancements in diagnosis. The main reason for this is that many newly diagnosed CRC patients will suffer from metastasis to other organs. Thus, the development of new therapies is of critical importance. Claudin-1 protein is a component of tight junctions in epithelial cells, including those found in the lining of the colon. It plays a critical role in the formation and maintenance of tight junctions, which are essential for regulating the passage of molecules between cells. In CRC, claudin-1 is often overexpressed, leading to an increase in cell adhesion, which can contribute to the development and progression of the disease. Studies show that high levels of claudin-1 are associated with poor prognosis in CRC patients and targeting claudin-1 may have therapeutic potential for the treatment of CRC. Previously, we have identified a small molecule that inhibits claudin-1 dependent CRC progression. Reported herein are our lead optimization efforts around this scaffold to identify the key SAR components and the discovery of a key new compound that exhibits enhanced potency in SW620 cells.

Relationship between loci of control and health-promoting behaviors in Pakistani women with polycystic ovary syndrome: coping strategies as mediators.

BACKGROUND/OBJECTIVES: Understanding the factors that promote healthy lifestyle behaviors in women with polycystic ovary syndrome is of substantial importance. Health-promoting lifestyle behaviors (HPLB) have been observed to be effective in managing various symptoms related to PCOS. This study aimed to examine the relationship between loci of control and health-promoting lifestyle behaviors in Pakistani women with polycystic ovary syndrome and the mediating role of coping strategies. METHOD: A correlational study was carried out with 145 unmarried women with polycystic ovary syndrome diagnosed by a gynecologist using the Rotterdam Criteria of 2003 (M age = 24.75 years). Participants were recruited from public sector hospitals in Lahore, Punjab, Pakistan and a series of hierarchical regression analyses were used to analyze results. RESULTS: Findings suggest that women with internal and powerful others locus of control use more active practical coping strategies and less active distractive coping strategies. These women also get more involved in health-promoting behaviors. On the other hand, those with a high level of chance locus of control use less active practical coping strategies and more active distractive coping strategies. In turn, they engage less in health-promoting behaviors. CONCLUSION: Health professionals should consider the effects of different types of locus of control and coping strategies when planning interventions for women with polycystic ovary syndrome.

Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells.

Despite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance have offered significant insight into the cancer malignancy and development of precise therapies. However, the heterogeneity of cancer and signaling pathways that regulate PC have posed limitations in the effective targeting of the PaCSCs. In this regard, the role for K-RAS, TP53, Transforming Growth Factor-ß, hedgehog, Wnt and Notch and other signaling pathways in PC progression is well documented. In this review, we discuss the role of PaCSCs, the underlying molecular and signaling pathways that help promote pancreatic cancer development and metastasis with a specific focus on the regulation of PaCSCs. We also discuss the therapeutic approaches that target different PaCSCs, intricate mechanisms, and therapeutic opportunities to eliminate heterogeneous PaCSCs populations in pancreatic cancer.

Cognitive behaviour therapy with compulsive hoarding: a single case study.

The current case study used cognitive behaviour treatment (CBT) for the management of a 35-year-old, married man who presented with complaint of compulsive hoarding. The complaint of compulsive hoarding (excessive acquisition, difficulty in discarding saved material and cluttering) was accompanied by feeling of anger, sad mood, low confidence, decreased sleep and appetite, poor problem solving ability, indecisiveness and interpersonal conflicts. The study was approved by the institutional research committee (Departmental Doctoral Programme Committee) and followed by the university research committee (Advance Studies and Review Board) as academic requirement for the duration of 2013-2020. Written consent was also taken from the individual to publish the results of the case. Twenty-eight CBT sessions of one-hour duration were conducted, over a period of six months. Management plan mainly comprised decision-making techniques, cognitive restructuring, behavioural experiments, problem solving and social skills training. The individual was assessed on pre, mid, post and follow up levels. Assessment showed significant decrease in the symptoms. The present case report will help clinicians dealing with individuals with compulsive hoarding and its associated features, effectively with CBT.

Dimensions of service quality in healthcare: a systematic review of literature.

PURPOSE: Various dimensions of healthcare service quality were used and discussed in literature across the globe. This study presents an updated meaningful review of the extensive research that has been conducted on measuring dimensions of healthcare service quality. DATA SOURCES: Systematic review method in current study is based on PRISMA guidelines. We searched for literature using databases such as Google, Google Scholar, PubMed and Social Science, Citation Index. STUDY SELECTION: In this study, we screened 1921 identified papers using search terms/phrases. Snowball strategies were adopted to extract published articles from January 1997 till December 2016. DATA EXTRACTION: Two-hundred and fourteen papers were identified as relevant for data extraction; completed by two researchers, double checked by the other two to develop agreement in discrepancies. In total, 74 studies fulfilled our pre-defined inclusion and exclusion criteria for data analysis. DATA SYNTHESIS: Service quality is mainly measured as technical and functional, incorporating many sub-dimensions. We synthesized the information about dimensions of healthcare service quality with reference to developed and developing countries. 'Tangibility' is found to be the most common contributing factor whereas 'SERVQUAL' as the most commonly used model to measure healthcare service quality. CONCLUSION: There are core dimensions of healthcare service quality that are commonly found in all models used in current reviewed studies. We found a little difference in these core dimensions while focusing dimensions in both developed and developing countries, as mostly SERVQUAL is being used as the basic model to either generate a new one or to add further contextual dimensions. The current study ranked the contributing factors based on their frequency in literature. Based on these priorities, if factors are addressed irrespective of any context, may lead to contribute to improve healthcare quality and may provide an important information for evidence-informed decision-making.

Increased trend of unnecessary use of radiological diagnostic modalities in Pakistan: radiologists perspective.

BACKGROUND: Over the past few years, a significant overuse of radiological investigations influenced the quality and cost of healthcare of the country as it may lead to non-compliance of the patient due to non-affordability and also may harm the patient in terms of radiation hazards. Pakistan, being a low-income, resource-constraint country, is facing financial impact on families as well as health system due to multiple reasons. OBJECTIVES: The purpose of study is to identify reasons of unnecessary use of radiological diagnostic modalities in Pakistani hospitals as perceived by radiologists. METHODS: A cross-sectional study was conducted on a total of all 105 radiologists, having at least 1 year experience of working in radiology, working in five tertiary care hospitals in Lahore. A self-constructed, self-administered, pretested 5-point Likert scale opinion-based questionnaire was administered after taking informed consent. It includes questions about excessive radiological use that may be attributed to the physicians, investigations, patients and other non-categorized causes. Results were analyzed using SPSS version 23. RESULTS: Since the assessment forms were handed over and collected from the radiologists in person, the response rate was 100%. Of a total of 105 respondents, 78 (74.28%) respondentsagreed that there is an actual increase, 25 (23.80%) respondents disagreed and 2 (1.90%) respondents were unsure. Most important reasons for increased usage of radiological investigations are 'need of accuracy of diagnosis' (P = 0.009), 'trend of physicians to repeat tests in order to confirm preset diagnoses' (P-value = 0.03), 'lack of knowledge about proper usage of radiological advances' (P-value = 0.005) and 'lack of proper clinical examination' (P-value = 0.04). CONCLUSION: Unnecessary use of radiological investigations is actually there as perceived by radiologists, which is attributed to inadequate knowledge, attitude and training of physicians to refer patients to radiological resources. This research can be a stepping stone for future researchers as it can be used for elaborating these causes individually and finding ways as to how each of these causes can be controlled and minimized to bring about a decline in excessive usage of these modalities for the betterment of the patients.

Evaluating quality standards' adherence in surgical care: a case study from Pakistan.

OBJECTIVE: To explore the extent of adherence to surgical quality standards and areas of improvement. DESIGN: Multi-method case study was done. Assessment of observed/actual and self-reported adherence to quality standards in surgical care was done on WHO's safe-surgery checklist. Client satisfaction through exit interviews assessed of all operated during 1 month. Semi-structured interviews of key informants were conducted to identify areas of improvements in surgical care in this hospital. SETTING: Conducted in a tertiary care teaching hospital in Lahore, Pakistan. PARTICIPANTS: Out of all 154 patients during 1 month were admitted with indications for surgery and 35.71% patients gave consent and participated in the study. OUTCOME MEASURE: Actual and reported adherence data were categorized in excellent, good, satisfactory and poor adherence to standards. For in-depth interviews, themes were identified from textual data. RESULTS: Overall activities in surgical department were performed well, patients were satisfied and hospital surgical mortality rate was zero but infection control measures needs attention and these practices were found poor with high re-operation and re-admissionrate (P-value < 0.001). Adherence to standards of surgical quality was inadequate in pre-operative, operative and post-op steps as assessed on the checklist but actual adherence was different from reported adherence by surgical care providers. CONCLUSION: This case study shows a complete picture of surgical care quality in a hospital of Pakistan. Discrepancy between perceived/reported adherence and actual practice was found. Patients' satisfaction is not a reliable outcome measure of surgical care quality.

Evaluation of biological potential of selected species of family Poaceae from Bahawalpur, Pakistan.

BACKGROUND: Oxidative stress as well as bacterial and fungal infections are common source of diseases while plants are source of medication for curative or protective purposes. Hence, aim of study was to compare the pharmacological potential of seven grass species in two different solvents i.e. ethanol and acetone. METHODS: Preliminary phytochemical tests were done and antioxidant activities were evaluated using ELISA and their IC50 values and AAI (%) were recorded. ANOVA was used for statistical analyses. DNA damage protection assay was done using p1391Z plasmid DNA and DNA bands were analyzed. Antimicrobial activity was done via disc diffusion method and MIC and Activity Index were determined. Cytotoxic activity was carried out using the brine shrimps' assay and LC50 values were calculated using probit analysis program. RESULTS: Phytochemical studies confirmed the presence of secondary metabolites in most of the plant extracts. Maximum antioxidant potential was revealed in DiAEE, DiAAE (AAI- 54.54% and 43.24%) and DaAEE and DaAAE (AAI- 49.13% and 44.52%). However, PoAEE and PoAAE showed minimum antioxidant potential (AAI- 41.04% and 34.11%). SaSEE, DiAEE and ElIEE showed very little DNA damage protection activity. In antimicrobial assay, DaAEE significantly inhibited the growth of most of the microbial pathogens (nine microbes out of eleven tested microbes) among ethanol extracts while DaAAE and ImCAE showed maximum inhibition (eight microbes out of eleven tested microbes) among acetone plant extracts. However, PoAEE and PoAAE showed least antimicrobial activity. F. oxysporum and A. niger were revealed as the most resistant micro-organisms. ImCEA and ImCAE showed maximum cytotoxic potential (LC50 11.004 ppm and 7.932 ppm) as compared to the other plant extracts. CONCLUSION: Fodder grasses also contains a substantial phenols and flavonoids contents along with other secondary metabolites and, hence, possess a significant medicinal value. Ethanol extracts showed more therapeutic potential as compared to the acetone extracts. This study provides experimental evidence that the selected species contains such valuable natural compounds which can be used as medicinal drugs in future.

Evaluation of antioxidant activity of leaves and fruits extracts of five medicinal plants.

Antioxidants acts as a defense mechanism that protects against oxidative damage caused by free radicals produced in the body. Medicinal plants are preferably used for various diseases in many countries. The studies were conducted to determine the antioxidant capacity of the ethanolic leaves and fruits extracts of Physalis minima, Withania somnifera, Datura inoxia, Solanum nigrum and Kigelia africana by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Quercetin was used as a standard antioxidant which shows 93.66% inhibition. Among the five selected plant species, the percentage of antioxidant activity of leaves extracts was found in order: P. minima > W. somnifera > S. nigrum > K. africana > D. inoxia and fruits extracts was in order: W. somnifera ≥ D. inoxia > P. minima > K. africana > S. nigrum respectively.

Assessment of phytochemicals, antioxidant, anti-hemolytic, anti-inflammatory and anti-cancer potential of flowers, leaves and stem extracts of.

OBJECTIVE: To evaluate phytochemicals and in vitro biological potential of flowers, leaves and stem extracts of Rosa arvensis. METHODS: Presence of twenty secondary metabolites was confirmed and then phenolic and flavonoid contents were quantified spectrophotometrically. Fourier Transform Infrared spectroscopy was conducted to ascertain functional groups and antioxidant potential was examined using 2,2-diphenyl-1-picrylhydrazyl scavenging activity, total antioxidant capacity and total reducing power assays. Human erythrocytes were used to assess anti-hemolytic activity and five bacterial strains were examined to determine antibacterial potential of plant extracts. Radish seeds were used to perform phytotoxic activity and cytotoxic potential was evaluated via brine shrimps and PC3 cell lines. RESULTS: Highest phenolic contents were detected in the methanolic extract of Rosa arvensis flower (RAFM) [(151.635 ± 0.005) gallic acid equivalent mg/g] and highest flavonoid contents in the chloroform leaf extract (RALC) [(108.228 ± 0.004) quercetin equivalent mg/g]. Fourier-transform infrared spectroscopy analysis showed the presence of wide range of functional groups. The antioxidant assays indicated highest DPPH scavenging activity [IC50 (23.5 ± 0.6) µg/mL] in the methanolic stem extract (RASM), highest total antioxidant capacity [(265.1 ± 0.9) µg/mL] in RAFM and highest reducing potential [(209.9 ± 0.6) µg/mL] in leaf extract (RALM). Highest anti-hemolytic activity [(90.0 ± 0.5) µg/mL] was recorded in RAFM and brine shrimp cytotoxicity potential [(52.3 ± 0.3) µg/mL] in RASM. The antimicrobial activity was detected highest [(21.1 ± 0.5) mm inhibition zones] in RALM against Streptococcus aureus. In the end, anti-inflammatory and anti-cancer activity results depicted less than 50 % inhibition in the methanolic extracts. CONCLUSIONS: Our findings will be helpful in designing pharmaceutical regimens and therefore, more studies can be recommended to isolate and characterize compounds associated with the biological activities of Rosa arvensis.

Characterization, anti-microbial, anti-oxidant and growth promoting effects of biogenically synthesized silver nanoparticles derived from Dicliptera bupleuroides Nees.

One of the most important areas of nanotechnology is the use of nanoparticles (NPs) for a variety of environmental and biological applications, with silver nanoparticles (Ag-NPs) gaining a lot attention due to their distinct properties. The current study deals with the synthesis of Ag-NPs from Dicliptera bupleuroides Nees leaf extract and to determine their antioxidant, antimicrobial potential and effects on wheat seed germination and growth. UV-Visible spectrum revealed a prominent absorption peak at 442 nm, elucidating the conformation of the Ag-NPs synthesis. Scanning electron microscopy (SEM) showed distinctive triangular, pyramidal, and irregular shape. X-ray diffraction (XRD) demonstrated their crystalline nature, with average crystallite size of the Ag-NPs measured at 20.52 nm. Fourier-transform infrared spectroscopy (FT-IR) further confirmed the presence of functional groups such as Phenols (O-H stretch), transition metal carbonyls N-H, ≡C-H, C ≡ N, C ≡ C, C-Cl, C-Br and O-H bonds on the surface Ag-NPs. The antibacterial activity of the Ag-NPs was most pronounced against Bacillus subtilis, with a zone of inhibition (ZOI) measuring 11 mm ± 0.57 at a concentration of 1000 µg/mL (45% inhibition). Likewise, Ag-NPs exhibited highest antioxidant potential (73.2%) at 100 µg/mL compared with standard (ascorbic acid) which showed (76%) at the same concentration. Furthermore, the effect of D. bupleuroides mediated Ag-NPs on wheat seeds growth and germination was recorded maximum at high concentrations (200-300 ppm). In conclusion, D. bupleuroides mediated Ag-NPs showed safe, cost effective and environmentally friendly synthesis which can be used as an antibacterial and antioxidant agent as well as for enhancing the growth and seed germination of crop seeds globally. RESEARCH HIGHLIGHTS: Nanotechnology is the study of nanoparticles for biological and environmental applications. Ag-NPs among other NPs have received broad attention because of their unique properties. D. bupleuroides Ag-NPs: 45% antibacterial, 73.2% antioxidant, enhance wheat germination. D. bupleuroides-mediated Ag-NPs are both cost-effective and environmentally beneficial.

Green solvent-based extraction of three Fabaceae species: A potential antioxidant, anti-diabetic, and anti-leishmanial agents.

The Fabaceae is renowned for its diverse range of chemical compounds with significant biological activities, making it a valuable subject for pharmacological studies. The chemical composition and biological activities of three Fabaceae species were investigated using methanol separately and in combination with dimethyl sulfoxide (DMSO) and glycerol for extraction. The results revealed the highest phenolic (49.59 ± 0.38 mg gallic acid equivalent/g), flavonoid (29.16 ± 0.39 mg rutin equivalent/g), and alkaloid (14.23 ± 0.54 mg atropine equivalent/g) contents in the Caesalpinia decapetala methanol extracts. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and DNA protection activity were the highest (0.88 ± 0.43 µg/mL IC50 and 2149.26 band intensity) in Albizia julibrissin methanol extracts. The α-amylase activity was highest in all methanol extracts (<15 µg/mL IC50 values), while the α-glucosidase inhibition potential was highest (<1 µg/mL IC50 value) in the methanol-glycerol and methanol-DMSO extracts. Pearson coefficient analysis showed a strong positive correlation between the DPPH and α-amylase assays and phytochemicals. Anti-leishmanial activity was observed in decreasing order: A. julibrissin (74.75 %) > C. decapetala (70.86 %) > Indigofera atropurpurea (65.34 %). Gas chromatography-mass spectrometry revealed 33 volatile compounds and, aamong these (Z)-9-octadecenamide was detected in the highest concentration ranging from 21.85 to 38.61 %. Only the methanol extracts of the examined species could be assessed for in vivo studies for immediate applications.

A preliminary study on the dynamics of serum color in perspective to hemoglobin and bilirubin in indigenous sheep of Pakistan.

The present study is the first of its kind being reported for an indigenous sheep breed of Pakistan with objectives to (a) assess the diagnostic efficacy of a human-based "serum hemolysis reference palette" for sheep serum, (b) deduce normal reference intervals (RIs) for hemoglobin (Hb) and bilirubin, and (c) devise a novel serum color chart for on-field estimation of Hb and bilirubin through color matching of sheep serum. Apparently, healthy Sipli sheep (n = 130) were bled twice attaining whole blood and serum samples (n = 260). The study animals were grouped on the basis of gender, that is, males (n = 51) and females (n = 79) and age, that is, G1 (up till 1 year) (n = 41), G2 (from 1 to 2 years) (n = 46), and G3 (from 2 to 3 years) (n = 43). None of the 260 serum samples of the sheep matched the color given on the human-based "hemolysis reference palette." The G1 animals revealed marked variation in their serum color. Hence, on the basis of RIs, the serum samples (n = 178) of adult sheep (G2 and G3) showing three main color bands were used in devising a novel serum Hb and bilirubin estimation chart for adult sheep serum. In conclusion, the human-based serum hemolysis palette is not valid for sheep serum. The RIs attained in the study could provide a yardstick for assessment of health in indigenous sheep breeds whereas the serum color chart may be of value in estimating Hb and bilirubin in a quick, reliable, and cheaper way for the resource-poor settings of the world.

A unified framework for activity recognition-based behavior analysis and action prediction in smart homes.

In recent years, activity recognition in smart homes is an active research area due to its applicability in many applications, such as assistive living and healthcare. Besides activity recognition, the information collected from smart homes has great potential for other application domains like lifestyle analysis, security and surveillance, and interaction monitoring. Therefore, discovery of users common behaviors and prediction of future actions from past behaviors become an important step towards allowing an environment to provide personalized service. In this paper, we develop a unified framework for activity recognition-based behavior analysis and action prediction. For this purpose, first we propose kernel fusion method for accurate activity recognition and then identify the significant sequential behaviors of inhabitants from recognized activities of their daily routines. Moreover, behaviors patterns are further utilized to predict the future actions from past activities. To evaluate the proposed framework, we performed experiments on two real datasets. The results show a remarkable improvement of 13.82% in the accuracy on average of recognized activities along with the extraction of significant behavioral patterns and precise activity predictions with 6.76% increase in F-measure. All this collectively help in understanding the users" actions to gain knowledge about their habits and preferences.

Biogenic synthesis of silver nanoparticles using Funaria hygrometrica Hedw. and their effects on the growth of Zea mays seedlings.

The biogenic synthesis of silver nanoparticles (AgNPs) is an important step in developing eco-friendly and environmentally stable tools for ameliorating crop growth. In the current study, AgNPs were synthesized using Funaria hygrometrica and characterized using ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The UV spectrum showed an absorption peak at 450 nm. SEM revealed an irregular and spherical morphology, FTIR spectroscopy indicated the presence of various functional groups, while XRD displayed peaks at 45.24°, 38.17°, 44.34°, 64.54°, and 57.48° 2θ. The effects of the F. hygrometrica-mediated AgNPs on maize growth and germination were assessed at 0, 100, 300, and 500 ppm. The germination percentage and relative germination rate were increased to 95% ± 1.83% and 100% ± 2.48% at 100 ppm of synthesized AgNPs and then declined at 300 and 500 ppm. The length, fresh weight, and dry matter of the root, shoot, and seedlings were highest at 100 ppm NPs. The plant height, root length, and dry matter stress tolerance indices were also the highest (112.3%, 118.7%, and 138.20% compared with the control) at 100 ppm AgNPs. Moreover, the growth of three maize varieties, that is, NR-429, NR-449, and Borlog, were assessed at 0, 20, 40, and 60 ppm F. hygrometrica-AgNPs. The results indicated the highest root and shoot length at 20 ppm AgNPs. In conclusion, seed priming with AgNPs enhances the growth and germination of maize and can ameliorate crop production globally. RESEARCH HIGHLIGHTS: Funaria hygrometrica Hedw.-mediated AgNPs were synthesized and characterized. Biogenic AgNPs influenced the growth and germination of maize seedlings. All growth parameters were highest at 100 ppm synthesized NPs.

Evaluation of potential inhibitory effects on acetylcholinesterase, pancreatic lipase, and cancer cell lines using raw leaves extracts of three fabaceae species.

The present study examined the biological potential and phytochemicals of Sophora mollis, Mucuna pruriens, and Indigofera atropurpurea methanolic leaf extracts. In vitro anti-acetylcholinesterase and anti-lipase assays were performed using different concentrations of plant extracts, and the IC50 values were determined. The cytotoxic potential of the selected plant extracts was assessed against HeLa, PC3, and 3T3 cell lines using an MTT assay. S. mollis leaf extract displayed the highest inhibition percentage (114.60% ± 19.95 at 1000 µg/mL) for the anti-acetylcholinesterase activity with a prominent IC50 value of 75.9 µg/mL. The anti-lipase potential was highest with the M. pruriens leaf extract (355.5 µg/mL IC50), followed by the S. mollis extract (862.7 µg/mL IC50). Among the cell lines tested, the cytotoxic potential of the I. atropurpurea extract (91.1 ppm IC50) against the PC3 cell line was promising. High-performance liquid chromatography revealed gallic acid, chlorogenic acid, caffeic acid, vanillic acid, rutin trihydrate, and quercetin dihydrate in varying concentrations in all plant species. The concentration of chlorogenic acid (69.09 ppm) was highest in M. pruriens, and the caffeic acid concentration (45.20 ppm) was higher in S. mollis. This paper reports the presence of bioactive therapeutic compounds in selected species of the Fabaceae family that could be micro-propagated, isolated, and utilized in pharmaceutical industries.

Claudin-1 interacts with EPHA2 to promote cancer stemness and chemoresistance in colorectal cancer.

Therapy resistance is the primary problem in treating late-stage colorectal cancer (CRC). Claudins are frequently dysregulated in cancer, and several are being investigated as novel therapeutic targets and biomarkers. We have previously demonstrated that Claudin-1 (CLDN1) expression in CRC promotes epithelial-mesenchymal transition, metastasis, and resistance to anoikis. Here, we hypothesize that CLDN1 promotes cancer stemness and chemoresistance in CRC. We found that high CLDN1 expression in CRC is associated with cancer stemness and chemoresistance signaling pathways in patient datasets, and it promotes chemoresistance both in vitro and in vivo. Using functional stemness assays, proteomics, biophysical binding assays, and patient-derived organoids, we found that CLDN1 promotes properties of cancer stemness including CD44 expression, tumor-initiating potential, and chemoresistance through a direct interaction with ephrin type-A receptor 2 (EPHA2) tyrosine kinase. This interaction is dependent on the CLDN1 PDZ-binding motif, increases EPHA2 protein expression by inhibiting its degradation, and enhances downstream AKT signaling and CD44 expression to promote stemness and chemoresistance. These results suggest CLDN1 is a viable target for pharmacological intervention and/or biomarker development.