Search

Background: While teleconsultation has proven feasible for adult cancer patients, its utility in childhood cancer care in India is unknown. This study assesses caregiver satisfaction, feasibility, and the economic impact of teleconsultation for children with cancer., Procedure: This mixed methods study was conducted in the pediatric cancer outpatient service at a tertiary care cancer center in India. Routine care teleconsultations were performed via telephone or email. Caregivers who received teleconsultations during the study period or 6 months prior were interviewed by phone. Data collected included demographic details, teleconsultation usage patterns, caregiver satisfaction, reasons for satisfaction or dissatisfaction, and cost savings. Logistic regression identified baseline characteristics associated with satisfaction. In-depth interviews were conducted in a separate cohort till thematic saturation., Results: Caregivers of 465 children were included for telephonic and eight for in-depth interviews Among the respondents, 72.8% (n = 339) were satisfied with teleconsultation, and 85.4% (n = 397) of those planned to continue using it. Significant reasons for satisfaction were cost and time savings, while difficulty explaining issues caused dissatisfaction. Multivariable analysis showed parental education above high school [OR: 1.59, p = 0.035] increased satisfaction likelihood, while a residential distance of greater than 100 km from the hospital [OR: 0.62, p = 0.033] decreased it. Median cost savings per visit was $24.2 (range: $1-$846). Cost savings did not determine satisfaction magnitude. Frequently cited themes included cost and time savings and the need for literacy to benefit from teleconsultation., Conclusions: Teleconsultation is feasible and effective for routine childhood cancer care, even in resource-constrained settings., (© 2025 Wiley Periodicals LLC.)

Gastrointestinal (GI) cancer represent significant health challenges, affecting the digestive system with often subtle symptoms that can delay diagnosis. GI cancers account for a higher global mortality rate than any other cancer, largely due to the limited availability of highly effective treatment options." Due to next-generation sequencing and new preclinical model tools, that we have learned more regarding its pathophysiology and molecular changes. Every molecular subtype has been characterised molecularly and new treatment targets have been found. Furthermore, tumour xenografts and organoids are grown from patients and are increasingly powerful resources for investigating GI patients' genetic evolution, identifying biomarkers, screening drugs, and conducting preclinical evaluations of personalised medicine approaches. Gastrointestinal (GI) cancer research is rapidly evolving, with recent advance-ments in precision medicine and immunotherapy offering new treatment options. Cutting-edge therapies, such as immune checkpoint inhibitors and targeted therapies like BRAF and HER2 inhibitors, are showing promise in treating specific types of GI cancers. These changes are making it possible for the age of precision medicine to use a mix of clinical, genome-based, and phenotype-based methods to diagnose and treat each GI patient individually. Clin-ical trials are exploring novel combinations of therapies to enhance survival rates and reduce side effects for patients with GI cancers, including colorectal, gastric, and pancreatic cancers. These developments are reshaping the future of gastrointestinal oncology. The purpose of this review is to study the current state of knowledge about predictive biomarkers, prospective novel targeted treatments, potential causes of conflicting trial outcomes, and the prospects for precision medicine in gastric cancer in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) remains a major challenge in developing effective treatments due to its complex pathophysiology, including the accumulation of amyloid-beta plaques and tau tangles. Small interfering RNA (siRNA) technology offers promise for targeted gene silencing, but effective delivery to the central nervous system remains a significant obstacle. Viral vectors have emerged as potent delivery vehicles for transporting siRNA to neural tissues. This review explores the utilization of viral vectors for siRNA delivery in AD, focusing on delivery strategies and challenges. We discuss the design and optimization of viral vectors, targeting strategies, and safety considerations. Additionally, we examine recent advancements and prospects for enhancing viral vector-mediated siRNA delivery in AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Triple-negative breast cancer (TNBC) is a subtype known for its aggressive nature, high rates of recurrence, and treatment resistance, largely attributed to the presence of breast cancer stem cells (BCSCs). Traditional therapies often struggle to eliminate BCSCs, which contributes to tumor recurrence. One promising strategy for addressing this challenge is targeting the Notch signaling pathway, which plays a critical role in the self-renewal and maintenance of BCSCs. DAPT, a potent γ-secretase inhibitor that down-regulates Notch, has limited use due to poor bio-distribution and off-target effects. To achieve the targeted delivery of DAPT to TNBC cells, we encapsulated DAPT in solid lipid nanoparticles (SLNs), and the surface of SLNs was further decorated with DLL4 and DR5 antibodies to produce DLL4-DR5-DAPT@SLNs (∼256 ± 3 nm). The developed DLL4-DR5-DAPT@SLNs have been characterized using various spectroscopy and microscopy techniques. The in vitro studies demonstrated that, DLL4-DR5-DAPT@SLNs can effectively internalize, showing excellent cytotoxicity and efficiently suppress cell migration and invasion by reducing the expression of Notch-1, promote apoptosis by increasing the expression of Caspase-8 and eventually inhibit the process of EMT via up-regulating the E-cadherin and down-regulating the vimentin expression at protein level. Further, in vivo studies demonstrated that DLL4-DR5-DAPT@SLNs exhibit targeted accumulation within tumors, resulting in a notable reduction in tumor size from 2.3 cm to 0.9 cm and a decrease in tumor volume from 2506.2 ± 104.6 mm 3 to 832.4 ± 93.1 mm 3 . The targeted treatment significantly reduced the overall tumor burden, contributing to the extension of long-term survival rates. The findings reveal that functionalization of DLL4 and DR5 significantly enhances the therapeutic delivery of DAPT to TNBC cells via simultaneously inhibiting the Notch signaling pathway and promoting apoptosis. The developed nanosystem addresses limitations associated with conventional therapies, such as insufficient targeting, systemic toxicity, and poor bioavailability. This study presents the innovative nanosystem as a potential treatment strategy for TNBC, aiming to enhance treatment efficacy and reduce off-target effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Three-dimensional (3D) models, such as tumor spheroids and organoids, are increasingly developed by integrating tissue engineering, regenerative medicine, and personalized therapy strategies. These advanced 3D in-vitro models are not merely endpoint-driven but also offer the flexibility to be customized or modulated according to specific disease parameters. Unlike traditional 2D monolayer cultures, which inadequately capture the complexities of solid tumors, 3D co-culture systems provide a more accurate representation of the tumor microenvironment. This includes critical interactions with mesenchymal stem/stromal cells (MSCs) and induced pluripotent stem cells (iPSCs), which significantly modulate cancer cell behavior and therapeutic responses. Most of the findings from the co-culture of Michigan Cancer Foundation-7 breast cancer cells and MSC showed the formation of monolayers. Although changes in the plasticity of MSCs and iPSCs caused by other cells and extracellular matrix (ECM) have been extensively researched, the effect of MSCs on cancer stem cell (CSC) aggressiveness is still controversial and contradictory among different research communities. Some researchers have argued that CSCs proliferate more, while others have proposed that cancer spread occurs through dormancy. This highlights the need for further investigation into how these interactions shape cancer aggressiveness. The objective of this review is to explore changes in cancer cell behavior within a 3D microenvironment enriched with MSCs, iPSCs, and ECM components. By describing various MSC and iPSC-derived 3D breast cancer models that replicate tumor biology, we aim to elucidate potential therapeutic targets for breast cancer. A particular focus of this review is the Transwell system, which facilitates understanding how MSCs and iPSCs affect critical processes such as migration, invasion, and angiogenesis. The gradient formed between the two chambers is based on diffusion, as seen in the human body. Once optimized, this Transwell model can serve as a high-throughput screening platform for evaluating various anticancer agents. In the future, primary cell-based and patient-derived 3D organoid models hold promise for advancing personalized medicine and accelerating drug development processes., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Purpose: Telemedicine use in healthcare is rising. However, infrastructural barriers may impede implementation in lower- and middle-income country settings. Patient perspectives regarding teleconsultation need to be explored. This study assesses the feasibility of teleconsultation among patients with cancer, patient satisfaction with its use, determinants of satisfaction, and its economic benefits., Methods: A cross-sectional telephonic interview-based study was conducted between February and September 2021 in a tertiary care cancer center in India. Adult patients with cancer or their caregivers who had availed of teleconsultation during the 6 months preceding the interview date were included. Teleconsultation was administered through email and telephone conversation. The research team developed an interview guide to elicit demographic details, satisfaction with teleconsultation, and the underlying reasons. Cost savings through teleconsultation were also recorded. Factors predicting subject satisfaction were identified by multivariable logistic regression., Results: During the study period, 195 subjects, including 84 patients (43.1%) and 111 caregivers (56.9%), were interviewed. The median patient age at diagnosis was 31 years. In our study, 147 (75.4%) patients/caregivers reported satisfaction with teleconsultations. The benefits cited included better access and follow-up (n = 173, 88.7%) and saving time and money (n = 164, 84.1%). In multivariable analysis, a higher patient age (more than 30 years) was the only factor predictive of less satisfaction with teleconsultation. The median cost savings were not a predictor of satisfaction., Conclusion: Teleconsultation is feasible and acceptable to most patients availing treatment in a tertiary oncology care setting in India. Patient and physician training for better communication may further improve the utility of this modality., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To explore the magnitude of sex bias and determinants of treatment abandonment (TA) in childhood cancer in India., Methods: Individual data of children (0-19 y) registered between January 1, 2017 and July 31, 2022, was compiled. TA was defined as defaulting curative intent treatment ≥4 wk. Defaulting treatment irrespective of intent ≥4 wk was defined as Treatment Default (TD). The primary outcome was the proportion of male-to-female children with TA. Secondary outcomes included the proportion of male-to-female children with upfront TA, TA at relapse, TD, TD-p (TD only in the palliative setting). The impact of clinico-demographic factors on TA was analysed using multivariable regression and propensity score matching (PSM)., Results: Three thousand two hundred eighty four patients were analysed. The overall male-to-female ratio (MFR) was 2.08 (95% CI 1.94-2.24). Of 2906 patients treated with curative intent, 415 (14·3%) abandoned treatment. TA was higher in females than males (16·4% vs. 13·3%; p = 0·022) with adjusted MFR of 0·81 (0·66-0·98). The adjusted MFR of TA for treatment-naïve and relapsed patients and TD were 0·73 (0·59-0·91), 1·13 (0·65-1·96) and 0·84 (0·71-1·00) respectively. Sex independently predicted TA on multivariable analysis. However, on PSM analysis including socio-economic variables, lower maternal education predicted higher TA in children with cancer (10·1% vs. 6%, p = 0·015)., Conclusions: Child sex predicted TA in childhood cancer in India with more females abandoning treatment. Maternal education is a more crucial factor predicting TA over child sex, when socio-economic factors were considered. Hence, policies promoting female education and gender equality may mitigate sex-based gaps in childhood cancer care., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

This study investigated the formulation and characterization of rebamipide nanocrystals (REB-NCs) to enhance the solubility and permeability of rebamipide, an anti-ulcer medication known for its low aqueous solubility and permeability, classified as BCS class IV. Employing high-pressure homogenization and wet milling techniques, we successfully achieved nanonization of rebamipide, resulting in stable nanosuspensions that were subsequently freeze-dried to produce REB-NCs with an average particle size of 223 nm. Comprehensive characterization techniques, including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) confirmed the crystalline nature of the nanocrystals and their compatibility with the selected excipients. The saturation solubility study revealed a remarkable three-fold enhancement in PBS pH 7.4 compared to rebamipide API, indicating the effectiveness of the nanocrystal formulation in improving drug solubility. Furthermore, 3D in-vitro permeability assessments conducted on Caco-2 cell monolayers demonstrated an noticeable increase in the permeability of REB-NCs relative to the pure active pharmaceutical ingredient (API), highlighting the promise of this formulation to enhance drug absorption. The dissolution profile of the nanocrystal tablets exhibited immediate release characteristics, significantly outperforming conventional formulations in terms of the dissolution rate. This research underscores the potential of nanomilling as a scalable, environment-friendly, and less toxic approach to significantly enhance the bioavailability of rebamipide. By addressing the challenges associated with the solubility and permeability of poorly water-soluble drugs, our outcome offers insightful information into developing efficient nanomedicine strategies for enhancing therapeutic outcomes.

Efficient telmisartan delivery for hypertension management requires the incorporation of meglumine and/or sodium hydroxide as an alkalizer in the formulation. Long-term use of powerful alkalis with formulation as part of chronic therapy can cause metabolic alkalosis, ulcers, diarrhea, and body pain. Here, we aimed to design a telmisartan formulation without alkalizers. Telmisartan properties were tailor-made by microfluidizer-based physical modification. After microfluidization, telmisartan nanosuspension was lyophilized to obtain telmisartan premix powder. The optimized telmisartan nanosuspension had an average particle size of 579.85 ± 32.14 nm. The lyophilized premix was characterized by FT-IR, DSC, and PXRD analysis to ensure its physicochemical characteristics. The solubility analysis of premix showed 2.2 times, 2.3 times, and 6 times solubility improvement in 0.1 N HCl, phosphate buffer pH 7.5, and pH 6.8 compared to pure telmisartan. A 3D in-vitro Caco-2 model was developed to compare apparent permeability of API and powder premix. It showed that the powder premix was more permeable than pure API. The tablet formulation prepared from the telmisartan premix showed a dissolution profile comparable to that of the marketed formulation. The technique present herein can be used as a platform technology for solubility and permeability improvement of similar classes of molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer (BC) is the second deadliest cancer after lung cancer. Similar to all cancers, it is also driven by a 3D microenvironment. The extracellular matrix (ECM) is an essential component of the 3D tumor micro-environment, wherein it functions as a scaffold for cells and provides metabolic support. BC is characterized by alterations in the ECM. Various studies have attempted to mimic BC-specific ECMs using artificial materials, such as Matrigel. Nevertheless, research has proven that naturally derived decellularized extracellular matrices (dECMs) are superior in providing the essential in vivo -like cues needed to mimic a cancer-like environment. Developing in vitro 3-D BC models is not straightforward and requires extensive analysis of the data established by researchers. For the benefit of researchers, in this review, we have tried to highlight all developmental studies that have been conducted by various scientists so far. The analysis of the conclusions drawn from these studies is also discussed. The advantages and drawbacks of the decellularization methods employed for generating BC scaffolds will be covered, and the review will shed light on how dECM scaffolds help develop a BC environment. The later stages of the article will also focus on immunogenicity issues arising from decellularization and the origin of the tissue. Finally, this review will also discuss the biofabrication of matrices, which is the core part of the bioengineering process.

In developing countries, informal sector is the primary job provider for a significant portion of the workforce. This study aims to analyze how jobs in the informal sector affect the unemployment dynamics of developing nations. To achieve this goal, we formulate a nonlinear mathematical model by categorizing the considered workforce into three distinct classes: unemployed, employed, and self-employed, and include a separate dynamic variable to represent vacancies within the informal sector. The proposed model is analyzed using the qualitative theory of dynamical systems. A threshold quantity known as the reproduction number is derived and using this, one can compute the job generation rate necessary to stabilize the system. It is observed that variations in the reproduction number lead to qualitative changes, such as transcritical (forward or backward) and saddle-node bifurcations in the formulated system. Moreover, we propose an optimal control problem to determine an optimal strategy for government policy implementation in enhancing the employment rate of unemployed individuals and promoting the self-employment of informal employees inside the informal sector. Further, the analytical findings are validated numerically. The obtained results suggest that promoting the self-employment of informal employees for job generation effectively reduces unemployment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Urothelial carcinoma (UC) is a common malignancy, predominantly affecting males. Many tumor cells use the interaction between programmed death-ligand 1 (PD-L1) and programmed death receptor (PD-1) to inactivate T-cells in the microenvironment and evade host immune response. Our study aims to evaluate the expression of PD-L1 in UC and correlate its expression with histomorphological parameters., Materials and Methods: After obtaining approval from the Institute Ethics Committee, we conducted a prospective observational study on transurethral resection of urinary bladder tumor (TURBT) and cystectomy specimens histopathologically diagnosed as UC between 2022 and 2023, comprising 50 cases. All standard protocol was followed and immunohistochemistry (IHC) was done using PD-L1 with rabbit anti-human PD-L1 monoclonal antibody (Clone: IHC411; Biogenics Inc., San Francisco, CA, USA).  Results: Among the 50 cases of UC, the majority were papillary type (35 cases), high grade (28 cases), and non-muscle invasive (30 cases). Among the cases studied, 15 of them showed PD-L1 positivity; 55% of the cases of muscle-invasive bladder cancer were found to be positive for PD-L1 out of which the results were statistically significant., Conclusion: PD-L1 expression by IHC staining can differentiate between muscle-invasive and non-muscle-invasive UC cases. This observation allows for further exploring the potential role of immune checkpoint inhibitors in adjuvant and neoadjuvant therapy, especially in muscle-invasive cases of UC., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Indira Gandhi Institute of Medical Sciences Patna issued approval L/EC/GIMS/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Gene therapy is a revolutionary approach aimed at treating various diseases by manipulating the expression of specific genes. The composition and formulation of ultra-deformable vesicles play a crucial role in determining their properties and performance as siRNA delivery vectors. In the development of ultra-deformable vesicles for siRNA delivery, careful lipid selection and optimization are crucial for achieving desirable vesicle characteristics and efficient siRNA encapsulation and delivery. The stratum corneum acts as a protective barrier, limiting the penetration of molecules, including siRNA, into the deeper layers of the skin. Ultradeformable vesicles offer a promising solution to overcome this barrier and facilitate efficient siRNA delivery to target cells in the skin. The stratum corneum, the outermost layer of the skin, acts as a significant barrier to the penetration of siRNA.These engineering approaches enable the production of uniform and well-defined vesicles with enhanced deformability and improved siRNA encapsulation efficiency. Looking ahead, advancements in ultra-deformable vesicle design and optimization, along with continued exploration of combination strategies and regulatory frameworks, will further drive the field of ultra-deformable vesicle-based siRNA delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Mucormycosis, attributed to a group of molds known as mucormycosis, is a rare yet life-threatening fungal infection often colloquially referred to as black fungus. While its incidence notably surged during the second wave of COVID-19 infections in India, it's essential to recognize that mucormycosis was a significant concern even before the advent of the pandemic. Understanding the prevalence and characteristics of this infection in the pre-COVID era provides a crucial context for evaluating its impact and dynamics during the pandemic. Multiple diagnostic methods, such as potassium hydroxide (KOH) mount, culture, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and histopathological examination (HPE), are available for identifying this lethal infection. The primary objective of this study is to ascertain the sensitivity of various diagnostic methods for mucormycosis and to analyze the comparative effectiveness of microbiological versus histopathological diagnoses. Methods We conducted a retrospective observational study spanning six months, from May 2021 to October 2021, encompassing all mucormycosis cases meeting the inclusion criteria and diagnosed via histopathological examination (HPE) in the departments of pathology and microbiology. Microbiological tests were performed prior to the histopathological examinations. Sensitivity was assessed through statistical analysis, and the relationship between microbiological and histopathological diagnoses was evaluated using the chi-square test. Results Biopsy samples of 77 patients were collected, comprising 56 male and 21 female patients. Regarding age distribution, most patients fell within the 41-60 age bracket, while the smallest proportion was over 60 years old. The sensitivity and specificity of histopathological diagnosis, confirmed with periodic acid-Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) staining, both recorded a flawless 100%. KOH mount sensitivity stood at 88.3%, while fungal culture and MALDI-TOF exhibited sensitivities of 75.3%. Histopathological analysis revealed that 17% of cases displayed minimal fungal hyphae alongside necrotic tissue, whereas 58% exhibited abundant fungal hyphae accompanied by inflammatory cells. Additionally, absolute neutrophilia was observed in 55% of cases. Conclusions In our study, histopathology and KOH mount emerged as not only compassionate but also cost-effective diagnostic tools for identifying mucormycosis. The economic aspect of these diagnostic methods is highlighted in the results section to provide a comprehensive understanding of their cost-effectiveness. Additionally, we utilized MALDI-TOF MS as a straightforward, economically viable, and expeditious method specifically for confirming the fungal subtype in mucormycosis cases. The rationale behind choosing either MALDI-TOF MS or KOH for the diagnosis is elucidated, contributing to a clearer interpretation of our diagnostic approach. Furthermore, our findings indicate that absolute neutrophilia consistently manifests in 55% of mucormycosis cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rani Singh et al.)

The present study hypothesises that the selective brain β2 receptor activation through β2-adrenoreceptor agonist (β2ARA), Formoterol (FMT), suppresses SNCA gene expression, a pathological hallmark of Parkinson's disease (PD) in brain. Further, it is also hypothesized that brain targeted delivery of Formoterol via polysorbate-80 surface modified solid lipid nanoparticles of Formoterol (FMT-SLNs-PS80) can improve its stability, therapeutic efficacy and avoid/reduce peripheral off-target side effects. FMT-SLNs-PS80 was prepared by solvent injection method, the formulation was optimized by using Box-Behnken design and characterized by measuring drug content, entrapment efficacy, particle size, zeta potentials and poly dispersibility. The FMT-SLNs-PS80, significantly decreases the SNCA expression, mitochondrial membrane damage and rotenone induced changes in oxidative (SOD, CAT, GSH and ROS) stress markers in SH-SY5Y cell lines. The ex vivo permeation study of the formulation using everted chicken ileum exhibited a steady state flux. The pharmacokinetic and tissue distribution studies of the formulation in rats showed a significant improvement in the kinetic parameters when compared to naïve FMT, further the formulation also improved the brain bioavailability of FMT. The anti-Parkinson's efficacy studies of the formulation in mice showed a significant neuroprotection against rotenone-induced changes in behavioural and biochemical parameters. Further, the histopathological analysis of mice brain confirms a significant neuroprotective benefit. The present study successfully establishes the brain targeted delivery and anti-Parkinson's therapeutic efficacy of FMT-SLNs-PS80., (© 2023. The Author(s).)

Nanotechnology provides effective methods for precisely delivering chemotherapeutics to cancer cells, thereby improving efficacy and reducing off-target side effects. The targeted delivery of nanoscale chemotherapeutics is accomplished by two different approaches, namely the exploitation of leaky tumor vasculature (EPR effect) and the surface modification of nanoparticles (NPs) with various tumor-homing peptides, aptamers, oligonucleotides, and monoclonal antibodies (mAbs). Because of higher binding affinity and specificity, mAbs have received a lot of attention for the detection of selective cancer biomarkers and also for the treatment of various types of cancer. Antibody-conjugated nanoparticles (ACNPs) are an effective targeted therapy for the efficient delivery of chemotherapeutics specifically to the targeted cancer cells. ACNPs combine the benefits of NPs and mAbs to provide high drug loads at the tumor site with better selectivity and delivery efficiency. The mAbs on the NP surfaces recognize their specific receptors expressed on the target cells and release the chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin-avidin interaction. This review also provides an overview of the many effects of the protein corona and the theranostic applications of ACNPs for the treatment of cancer., Competing Interests: The authors declare no competing interests., (Copyright © 2023, Kumari et al.)

Early-season agricultural drought is frequent over South Asian region due to delayed or deficient monsoon rainfall. These drought events often cause delay in sowing and can even result in crop failure. The present study focuses on monitoring early-season agricultural drought in a semi-arid region of India over 5-year period (2016-2020). It utilizes hydro-climatic and biophysical variables to develop a combined drought index (CDI), which integrates anomalies in soil moisture conditions, rainfall, and crop-sown area progression. Synthetic aperture radar (SAR)-based soil moisture index (SMI) represents in situ measured soil moisture with reasonable accuracy (r=0.68). Based on the highest F1-score, SAR backscatter in VH (vertical transmit-horizontal receive) polarization with specific values for parameter threshold (-18.63 dB) and slope threshold (-0.072) is selected to determine the start of season (SoS) with a validation accuracy of 73.53%. The CDI approach is used to monitor early-season agricultural drought and identified drought conditions during June-July in 2019 and during July in 2018. Conversely, 2020 experienced consistently wet conditions, while 2016 and 2017 had near-normal conditions. Overall, the study highlights the use of SAR data for early-season agricultural drought monitoring, which is mainly governed by soil moisture-driven crop-sowing progression. The proposed methodology holds potential for effective monitoring, management, and decision-making in early-season agricultural drought scenarios., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

CIM-Saumya is an improved, methyl chavicol rich variety of Ocimum basilicum (Family-Lamiaceae), developed by Council of Scientific and Industrial Research-Central Institute of Medicinal and Aromatic Plants. This plant possesses analgesic, anti-ulcerogenic, anti-inflammatory, anti-oxidant, cardiac stimulant, Central Nervous System depressant, hepatoprotective and immunomodulator activities due to the presence of various phytoconstituents. Among them rosmarinic acid, caffeic acid and ferulic acid are the three major phenolic compounds responsible for its therapeutic utility. These compounds are produced in very low amounts in the in vivo plants. Therefore, the present study has been conducted for establishment of cell suspensions, optimization of inoculums size, growth kinetics and screening of elicitor and precursors for the accumulation of cell biomass and the production of the three important phenolic compounds in cell suspension of O. basilicum (CIM-Saumya). Leaf derived friable callus was used for establishing the cell suspension in liquid Murashige and Skoog's medium fortified with 1 g/L casein hydrolysate + 2.26 µM 2,4-dichlorophenoxyacetic acid + 0.465 µM kinetin + 2.68 µM naphthalene acetic acid. The growth kinetic analysis pattern of cell suspension revealed the maximum biomass increments (% BI = 486.7) and production of RA 8.086 mg/g dry weight was found in 30th day harvested cells. Whereas, the other two phenolic compounds i.e. ferulic acid (0.0125 mg/g dry weight) and caffeic acid (0.38 mg/g dry weight) was recorded highest on 25th day of growth cycle. In the present study, one biotic elicitor i.e. yeast extract and three precursors [peptone, tryptone and lactalbumin hydrolysate] were tested, among them, lactalbumin hydrolysate (100 mg/L; added at 16th day) treated cells recorded highest estimated phenolic compounds yield (251.5 mg/L; 6.81 fold compared to the control) and biomass increments i.e. % BI = 1207 with 1.85 fold compared to the control. The highest rosmarinic acid content i.e. 25.47 mg/g DW (4.4 fold compared to the control) and 24.42 mg/g dry weight (4.1 folds compared to the control) was noticed in 30th day harvested cells treated with yeast extract (1 g/L on 0 day) and lactalbumin hydrolysate (100 mg/L added on 16th day), respectively. While caffeic acid content (0.91 mg/g dry weight) showed 2.9 folds higher compared to the control in cells treated with peptone 200 mg/L added on 16th day of culture cycle. All the treated cells showed enhanced phenylalanine ammonia-lyase enzyme activity with highest specific activity in lactalbumin hydrolysate followed by tryptone, peptone, and yeast extract., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01316-6., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Escherichia coli infection is the major bacterial disease affecting the poultry industry and the continuous use of antibiotics in poultry farming has resulted in antibiotic resistance. So this study was planned to evaluate the use of an ecologically safe alternative to fight against infections. The leaf gel of the Aloe vera plant was selected based on its antibacterial activity assessed in in-vitro tests. The objective of the present study was to evaluate the effect of A. vera leaf extract supplementation on the severity of clinical signs and pathological lesions, mortality rate, levels of antioxidant enzymes, and immune response in experimentally E. coli-infected broiler chicks. Broiler chicks were supplemented with aqueous Aloe vera Leaf (AVL) extract @ 20 ml per liter of water from day one of age. After seven days of age, they were experimentally infected with E. coli O78 @ 10 7 CFU/0.5 ml intraperitoneally. Blood was collected at weekly intervals up to 28 days and assayed for antioxidant enzyme assays, and humoral and cellular immune response. The birds were observed daily for clinical signs and mortality. Dead birds were examined for gross lesions and representative tissues were processed for histopathology. The activities of antioxidants, Glutathione reductase (GR), and Glutathione-S-Transferase (GST) were significantly higher than the control infected group. The E. coli-specific antibody titer and Lymphocyte stimulation Index were comparatively higher in the AVL extract-supplemented infected group as compared to the control infected group. No considerable change was noted in the severity of clinical signs and pathological lesions, and mortality. Thus, Aloe vera Leaf gel extract enhanced the antioxidant activities and cellular immune responses of infected broiler chicks to combat this infection., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

India generates 126.6 and 42 million tons of Rice straw (RS) and Rice husk (RH) annually, respectively. These agro-processing wastes feedstock are dumped in landfills or burnt, releasing toxic gases and particulate matter into the environment. This paper explores the valorization of these wastes feedstock into sustainable, economic products. We compare these wastes as matrices for lipase immobilization. These matrices were characterized, different parameters (pH, temperature, ionic strength, and metal ion cofactors) were checked, and the selected matrix was analyzed for reusability and hydrolysis of vegetable oils. Lipase immobilized Rice straw (LIRS) showed the highest activity with 72.84% protein loading. Field emission scanning electron microscopy (FESEM) demonstrated morphological changes after enzyme immobilization. FTIR showed no new bond formation, and immobilization data was fitted to Freundlich adsorption isotherm (with K  = 12.18 mg/g, n F  = 4.5). The highest activity with protein loading, 91.05%, was observed at pH 8, 37 °C temperature, 50 mM ionic strength, and lipase activity doubled in the presence of Mg 2+ ions. The LIRS retained 75% of its initial activity up to five cycles and efficiently hydrolyzed different oils. The results reflected that the LIRS system performs better and can be used to degrade oily waste.

One of the most significant threats in Parkinson's disease (PD) is neurodegeneration. Neurodegeneration at both nigral as well as non-nigral regions of the brain is considered responsible for disease progression in PD. The key factors that initiate neurodegeneration are oxidative stress, neuroinflammation, mitochondrial complex-1 inhibition, and abnormal α-synuclein (SNCA) protein aggregations. Nigral neurodegeneration results in motor symptoms (tremor, bradykinesia, rigidity, shuffling gait, and postural instability) whereas; non-nigral neurodegeneration is responsible for non-motor symptoms (depression, cognitive dysfunctions, sleep disorders, hallucination, and psychosis). The available therapies for PD aim at increasing dopamine levels. The medications such as Monoamine oxidase B (MAO-B) inhibitors, catechol o-methyltransferase (COMT) inhibitors, Dopamine precursor (Levodopa), dopamine agonists, and dopamine reuptake inhibitors drastically improve the motor symptoms and quality of life only in the early stages of the disease. However, dopa resistant motor symptoms (abnormality in posture, speech impediment, gait, and balance problems), dopa resistant non-motor signs (sleep problems, autonomic dysfunction, mood, and cognitive impairment, pain), and drug-related side effects (motor fluctuations, psychosis, and dyskinesias) are considered responsible for the failure of these therapies. Further, none of the treatments, alone or in combination, are capable of halting the disease progression in the long run. Therefore, there is a need to develop safe and efficient neuroprotective agents, which can slow or stop the disease progression for the better management of PD. In this review, an effort has been made to discuss the various mechanisms responsible for progressive neurodegeneration (disease progression) in PD and also multiple strategies available for halting disease progression., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022., Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-., Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p  = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed., Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination., Funding: None., Competing Interests: We declare no competing interests., (© 2022 The Authors.)

Knowledge regarding the lesser common breast tumours, including malignant papillary neoplasms and glycogen-rich clear cell carcinoma, is limited. Overall, cases of papillary carcinoma of the breast fare better than invasive breast carcinoma, from the data available in literature. Glycogen-rich clear cell carcinoma is characterized by the presence of clear cells, having mostly a poorer prognosis. We hereby present three such cases which would add to the existing available information. Case 1 is a 79-year-old female who presented with a left breast lump and bloody nipple discharge. Mammography suggested malignant lesion, with FNAC suspicious of malignancy. Surgery was done and histopathological examination showed irregular islands of tumour cells having papillary fronds with absence of myoepithelial layer. Immunohistochemically, the tumour was GATA3, CK7, ER, PR positive, HER2 negative, with Ki67 index 10%. The case was diagnosed as Solid papillary carcinoma. Case 2 is a 57-year-old female presenting with a left breast lump along with bloody nipple discharge. Mammography and FNAC were in favour of malignancy. Trucut biopsy was done, microscopy revealing a tumour having >90% papillary architecture with infiltrative pattern. Features were suggestive of Invasive breast carcinoma with papillaroid features. The tumour was GATA3, CK7, ER, PR positive, HER2 negative, with Ki67 index 15%. Case 3 is a 70-year-old female presenting with a right breast lump with nipple retraction. Mammography and FNAC were suggestive of malignancy. Trucut biopsy followed by microscopy revealed polygonal tumour cells with clear cytoplasm in nested pattern, showing positive staining for Periodic Acid Schiff. Immunostaining showed GATA3 positive, PAX8 negative, ER and PR positive, HER2 negative, and Ki67 index 20%. A diagnosis of Invasive breast carcinoma with Glycogen-rich clear cell pattern was made. Identifying these rare entities is important along with assessing hormone status for avoiding overtreatment and undertreatment and applying appropriate targeted therapies., (Copyright © 2024 Nigerian Medical Association.)

The β-diketo-modified isoxazole derivative of curcumin (IOC) is well renowned for its anticancer, antioxidant, antimalarial, antiproliferative, and many other biological activities. With the aim of obtaining fundamental knowledge on the photophysics of IOC, the present work was directed toward delineating those at different pH environments and studying the degradation profiles of IOC at five different pH values. Because one of the primary drawbacks of curcumin is its rapid degradation at physiological conditions, the studies showed that the problem could be resolved, as the IOC molecule was extremely stable even in a highly alkaline medium. Further, in order to encounter the problems associated with the low solubility of IOC in aqueous media, β-CD (β-cyclodextrin) was used and calculations of the thermodynamic parameters revealed that the process of development of the host-guest inclusion complex was highly spontaneous in nature. The synthesis of the IOC:β-CD inclusion complex has also been accomplished in the solid state, and the solid formed has been characterized using various physicochemical techniques. Finally, while variations in the pH as well as addition of foreign metal ions in +1 and +2 oxidation states showed minimal effect on the photophysics of the IOC:β-CD inclusion complex, antiproliferative studies performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays revealed their nontoxic nature on fibroblast L929 normal cell lines and extremely toxic activity on human lung cancer A549 cell lines.

Cranial vault defects are either congenital or acquired in origin. Cranioplasty is most commonly done in patients after trauma, decompressive craniectomies, tumor resections, infections or because of congenital malformations. The purpose of a Cranioplast is to protect the underlying brain tissues, reduce pain, and to improve the calvarial contour, symmetry, and esthetics. Rehabilitation of these defects possesses a challenge to the surgical team and prosthodontist. With advancement in three-dimensional (3D) engineering technology, the use of rapid prototyping technology (RPT) can be used in the fabrication of 3D skull eliminating conventional impression for recording defect region. Custom-made cranial prosthesis now can be fabricated using the conventional method of wax-up and lost-wax method. Case 1 had a history of road traffic accident followed by decompressive craniectomy, which led to frontoparietotemporal defect of the right side. The 3D model was fabricated using RPT technology. The wax pattern fabricated on 3D prototyped skull was contoured using digital photographic superimposition method. Case 2 had a history of trauma on the head causing intracerebral hemorrhage followed by decompressive craniectomy which led to frontoparietotemporal defect of the right side. The 3D model was fabricated using RPT. The wax pattern fabricated on 3D prototyped skull was contoured using the compass method. The use of these methods with the added advantage of RPT resulted in prosthesis with good esthetics and better fit. The contour of the prosthesis was replicated in the same manner as compared to the contralateral side. These techniques are easy to use and are less time consuming and had few chances of errors., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 National Journal of Maxillofacial Surgery.)

Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gamma-secretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss Solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis., (© 2021 The Authors.)

Lactic acid bacteria (LAB) are known for their probiotic properties, but only a few strains produce riboflavin. We evaluated the probiotic properties of four riboflavin-producing strains of Lactobacillus plantarum (BBC33, BBC32A, BIF43, and BBC32B) by using in vitro assessment and carried out multivariate principal component analysis (PCA) to select the best strain. Safety, antioxidant, and exopolysaccharide-producing properties were also studied. Lact. plantarum BBC33 showed better probiotic potential, followed by strain BIF43. Lact. plantarum BBC32A degraded mucin and excluded as a potential probiotic candidate. Lact. plantarum BIF43, BBC33, and BBC32A tolerated simulated gastrointestinal conditions and their overnight cell-free culture supernatants (CFSs, pH 4.0-4.3) inhibited the growth of Escherichia coli AF10, Salmonella Typhi MTCC98, Bacillus cereus NCDC250, and Pseudomonas aeruginosa NCDC105. Lact. plantarum BIF43 and BBC33 did not degrade mucin, adhered to human epithelial colorectal adenocarcinoma Caco-2 cells (22-25%), and aggregated with indicators (30-50%). Moreover, both were non-hemolytic and sensitive to most antibiotics tested. Of the two selected strains, BIF43 showed better exopolysaccharides (EPS) producing phenotype. The CFSs of all strains showed high (85-93%) 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. PCA confirmed the results obtained from in vitro probiotic experiments and supported the selection of Lact. plantarum BIF33 and BBC43, as potential probiotics.

In this work, Ru x Pd y alloy nanoparticles were uniformly decorated on a two-dimensional reduced graphene oxide (rGO) sheet by an in situ chemical co-reduction process. The resulting products were characterized by various physiochemical techniques such as X-ray diffraction, Raman spectroscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma atomic absorption spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy. Further, the synthesized Ru x Pd y @rGO nanocomposites have been employed as a heterogeneous catalyst for three different catalytic reactions: (1) dehydrogenation of aqueous ammonia borane (AB); (2) hydrogenation of aromatic nitro compounds using ammonia borane as the hydrogen source, and (3) for the synthesis of aromatic azo derivatives. The present work illustrates the sustainable anchoring of metal nanoparticles over the surface of rGO nanosheets, which could be used for multifarious catalytic reactions., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

The naturally occurring polyphenolic compound curcumin has shown various medicinal and therapeutic effects. However, there are various challenges associated with curcumin, which limits its biomedical applications, such as its high degradation rate and low aqueous solubility at neutral and alkaline pH. In the present study, efforts have been directed towards trying to resolve such issues by encapsulating curcumin inside the micelles formed by imidazolium-based surface-active ionic liquid (SAIL). The shape and size of the micelles formed by the SAIL have been characterized by using DLS analysis as well as TEM measurements. The photo-physics of curcumin in the presence of ionic liquid (IL) and also with the addition of salt (NaCl) has been explored by using different optical spectroscopic tools. The time-dependent absorption studies have shown that there is relatively higher suppression in the degradation rate of curcumin after encapsulation by the imidazolium-based SAIL in an aqueous medium. The TCSPC studies have revealed that there is deactivation in the nonradiative intramolecular hydrogen transfer process of curcumin in the presence of IL micelles as well as with the addition of salt. Furthermore, the time-dependent fluorescence anisotropy measurement has been carried out to figure out the location of curcumin inside the micellar system. In order to correlate all experimental findings, density functional theory (DFT) and classical molecular dynamics (MD) simulations at neutral pH media have been performed. It has been found that the van der Waals force of interactions plays a major role in the stabilization of curcumin in the micelles rather than the coulombic forces. It also has been observed that the van der Waals interactions remain unaffected in the presence of salt. However, as revealed by the MD simulation results, the micelles are found to be more compact in size after the addition of salt. The RMSD results show that the micelles formed by the SAIL achieve greater stability after a particular time constraint. Our results have divulged that the SAIL could act as a promising drug delivery system., Competing Interests: The authors declare no competing financial interest.

Introduction: α-synuclein (SNCA), a major component of Lewy body is a pathological hallmark of Parkinson's disease (PD). Mutations in the SNCA gene cause misfolding and aggregation of SNCA protein, which results in neurodegeneration. Several studies have established the neuroprotective benefits of β2-adrenoreceptor (β2AR) agonists in PD However, β2AR agonists are associated with peripheral side effects- tachycardia, palpitation, pulmonary edema, myocardial ischemia, and cardiac arrhythmia due to βARactivation in peripheral tissues. PD therapy with β2AR agonists, therefore, warrants a brain-specific delivery., Area Covered: This review highlights the SNCA mediated neurodegenerative pathways in PD and various treatment strategies under investigation to lower SNCA gene expression, primarily focusing on β2AR mediated pathway. The review also discusses the beneficial and side effects of β2AR agonists in PD treatment by reviewing clinical trials, epidemiological studies, and meta-analysis data. Here we depict the need to develop a novel drug delivery system to achieve brain-specific delivery of β2AR agonists to overcome peripheral side effects and also propose various nano delivery strategies to achieve the same., Expert Opinion: Brain targeted delivery of β2AR agonists via various nano delivery systems will significantly downregulate SNCA gene expression in PD and also overcomes peripheral side effects of β2AR agonists.

The present study was undertaken to investigate the effect of aqueous Withania somnifera root (WSR) extract in broiler chicks experimentally infected with Escherichia coli O78 @ 10 7  CFU/0.5 ml intraperitoneally. Clinical signs and mortality due to colibacillosis observed in infected chicks were mild and lasted for short duration in WSR extract supplemented group as compared with the nonsupplemented group. A significant increase in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, and creatine phosphokinase activities and a decrease in total protein and albumin concentrations were observed in the infected groups, though these changes were of lower magnitude in WSR extract supplemented group. A significantly higher activity of oxidative blood parameters such as superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase enzymes were noticed in WSR extract supplemented group. The WSR extract supplemented group revealed significantly higher E. coli-specific antibody titer and enhanced lymphocyte proliferation response as compared with the nonsupplemented group. The gross and histopathological lesions of colibacillosis were mild in the WSR extract-supplemented infected group as compared with the nonsupplemented infected group. Withania somnifera root extract supplementation produced 31.48 and 34.38% protection in the gross and histopathological lesions in E. coli infected chicks, respectively. It is concluded that supplementation of 20% WSR extract @ 20 ml/L of water caused a reduction in the severity, mortality, and recovery period of E. coli infection and enhanced the humoral and cellular immune responses suggesting its protective effect on limiting the pathology of E. coli infection in broiler chickens., (Copyright © 2019. Published by Elsevier Inc.)

Triple-negative Breast Cancer (TNBC) is the most aggressive and prevailing breast cancer subtype. The chemotherapeutics used in the treatment of TNBC suffer from chemoresistance, dose-limiting toxicities and off-target side effects. As a result, conventional chemotherapeutics are unable to prevent tumor growth, metastasis and result in failure of therapy. Various new targets such as BCSCs surface markers (CD44, CD133, ALDH1), signaling pathways (IL-6/JAK/STAT3, notch), pro and anti-apoptotic proteins (Bcl-2, Bcl-xL, DR4, DR5), hypoxic factors (HIF-1α, HIF-2α) and drug efflux transporters (ABCC1, ABCG2 and ABCB1) have been exploited to treat TNBC. Further, to improve the efficacy and safety of conventional chemotherapeutics, researchers have tried to deliver anticancer agents specifically to the TNBCs using nanocarrier based drug delivery. In this review, an effort has been made to highlight the various factors responsible for the chemoresistance in TNBC, novel molecular targets of TNBC and nano-delivery systems employed to achieve sitespecific drug delivery to improve efficacy and reduce off-target side effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Absolute lymphocyte count (ALC) has been associated with overall survival (OS) and event-free survival, but we do not know if ALC is associated with minimal residual disease (MRD) at the end of induction (EOI) and whether it can be used as surrogate marker in resource limited settings. Immunological differences between MRD-positive and MRD-negative B ALL patients at the EOI are not known at present. This prospective study evaluated the association of ALC and peripheral blood lymphocyte subset percentage at the EOI with MRD. ALC was done at baseline, day 8, and day 15 and at EOI. Assessment for MRD and peripheral blood lymphocyte subset was done at EOI. In 2-year study duration, 197 B cell acute lymphoblastic leukemia (ALL) patients were recruited out of which 150 were analyzed. Peripheral lymphocyte subset percentage was available for 58 patients. We found that ALC at baseline, day 8, day 15, and EOI was not associated with MRD. Day 8 ALC was significantly higher in poor steroid responders (day 8 blasts > 1 × 10 9 cells/l) ( p  < 0.0001). At the EOI, CD4 - CD8 + cell percentage in peripheral blood were significantly higher in MRD-positive patients than MRD-negative patients ( p  = 0.01). Our study suggests that ALC at any point is not a surrogate marker for MRD. Immunologically MRD-positive and MRD-negative patients differ in CD4 - CD8 + cells. The role of CD8 + T and TCRαβCD3 + T cells in eliminating residual leukemic cells need to be studied further by functional assays.

Purpose: To report our 5-year experience with intra-arterial chemotherapy (IAC) in the intravitreal chemotherapy (IvitC) era., Methods: Retrospective review of retinoblastoma treated with primary unilateral IAC in the IvitC era (2012-2017)., Results: There were 34 eyes treated with IAC alone versus 20 eyes treated with IAC plus IvitC for vitreous seeds. IAC (IAC alone vs. IAC plus IvitC) consisted of melphalan (41 vs. 10%) or melphalan plus topotecan (59 vs. 90%, p = 0.03). IvitC consisted of melphalan (60%) or melphalan plus topotecan (40%). Tumor control and globe salvage were achieved in 100% of group B and C eyes without IvitC. Despite more extensive vitreous seeds in the IvitC group ( p < 0.01), comparison of IAC alone versus IAC plus IvitC revealed no difference in tumor control for group D (88 vs. 69%, p = 0.36) or group E (67 vs. 100%, p = 0.25) and no difference in globe salvage for group D (88 vs. 69%, p = 0.36) or group E (58 vs. 57%, p = 0.39)., Conclusions: IAC is effective as primary therapy for unilateral group B, C, D, and E retinoblastoma. IvitC is an important adjuvant therapy to achieve comparable globe salvage rates for group D and E eyes with persistent active vitreous seeds.

Objective: There have been no long-term studies on trends in antibiotic resistance (ABR) on a national scale in India. Using a private laboratory network, the ABR patterns of organisms most commonly associated with bacteremia, obtained from patients across India between 2008 and 2014, were examined., Methods: A retrospective study of patient blood cultures collected over a 7-year period (January 1, 2008-December 31, 2014) was conducted. Data on the microorganism(s) identified and their antimicrobial susceptibility were obtained from SRL Diagnostics (Mumbai, India)., Results: Of 135268 blood cultures, 18695 (14%) had at least one identified pathogen. In addition to continual high rates of methicillin-resistant Staphylococcus aureus (MRSA; approximately 44.2%), high resistance to nalidixic acid among Salmonella Typhi (98%) was observed, and carbapenem resistance increased in both Escherichia coli (7.8% to 11.5%; p=0.332) and Klebsiella pneumoniae (41.5% to 56.6%; p<0.001). Carbapenem resistance was also stable and high for both Acinetobacter species (approximately 69.6%) and Pseudomonas aeruginosa (approximately 49%). Resistance was also detected to colistin in the Gram-negatives and to vancomycin and linezolid in S. aureus., Conclusion: Increasing resistance to antibiotics of last-resort, particularly among Gram-negatives, suggests an urgent need for new antibiotics and improved antimicrobial stewardship programs in India., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Health-related quality of life (HRQOL) in retinoblastoma survivors was assessed using parent proxy report of PedsQL(TM) 4.0 generic core scale. One hundred twenty-two parents of retinoblastoma survivors filled the questionnaire satisfactorily. This was compared with parent-reported HRQOL of 50 siblings. The median age of survivors was 98 (range, 60-247) months and male:female ratio was 2:1. The overall parent-reported HRQOL was significantly worse in survivors as compared to controls (74.4 ± 8.5 vs. 85.1 ± 4.6, P < 0.001). All health domains were significantly affected when compared with controls. None of the baseline and treatment-related factors predicted HRQOL., (© 2016 Wiley Periodicals, Inc.)

Background: With current modalities, cure rates of retinoblastoma are high and hence the number of survivors is increasing. However, data on quality of life (QOL) are minimal., Procedure: We analyzed QOL in 122 retinoblastoma survivors using the PedsQL(TM) 4.0 generic core scale. The self-reported questionnaire was filled by children of more than 5 years of age who had completed treatment for more than 12 months. The questionnaire consists of 23 questions on physical, social, emotional, and school domains on a scale from 0 to 4. This was converted to a scale from 0 to 100, where higher values represented better QOL. The QOL was compared with 50 siblings. Factors predicting the QOL were assessed., Results: The median age of retinoblastoma survivors was 98 months (range 60-247) and 68% were males. Overall QOL was significantly poorer in retinoblastoma survivors as compared with the controls. The emotional health domain of QOL was significantly affected. Difficulties in maintaining friendships and competing were reported in the social health domain. The school health domain showed significantly higher absenteeism. However, the physical health domain, including household work, exercise, and self-care, was similar in both the groups. Lower age at diagnosis (≤ 18 months) predicted better QOL (P = 0.05), whereas age at assessment, sex, IRSS stage, and previous surgery and radiotherapy were not predictive of poor QOL., Conclusions: We found a significantly poorer QOL in retinoblastoma survivors with the psychosocial health domain being more affected than the physical domain. Age less than 18 months at diagnosis predicted better QOL., (© 2015 Wiley Periodicals, Inc.)

In this work, gum acacia (GA)/poly(sodium acrylate) semi-interpenetrating polymer networks (Semi-IPN) have been fabricated via free radical initiated aqueous polymerization of monomer sodium acrylate (SA) in the presence of dissolved Gum acacia (GA), using N,N'-methylenebisacrylamide (MB) as cross-linker and potassium persulphate (KPS) as initiator. The semi-IPNs, synthesized, were characterized by various techniques such as X-ray diffraction (XRD), thermo gravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy. The dynamic water uptake behavior of semi-IPNs was investigated and the data were interpreted by various kinetic models. The equilibrium swelling data were used to evaluate various network parameters. The semi-IPNs were used as template for the in situ preparation of silver nanoparticles using extract of Syzygium aromaticum (clove). The formation of silver nanoparticles was confirmed by surface plasmon resonance (SPR), XRD and transmission electron microscopy (TEM). Finally, the antibacterial activity of GA/poly(SA)/silver nanocomposites was tested against E. coli., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Bioreduction of metal ions for the synthesis of stable nanoparticles (NPs) in physiological environment has been a great challenge in the field of nanotechnology and its application. In the present study, well-defined biofunctionalized gold nanoparticles (AuNPs) were developed following a biomimetic approach for an enhanced anticancer activity. The fucoxanthins-capped crystalline AuNPs showed a particle size of 14 nm. The temperature-mediated biosynthesized NPs were characterized by UV-vis, dynamic light scattering, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. The cytotoxicity of the NPs was analyzed on liver (HepG2) and lung (A549) cancerous cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay infers that the biofunctionalized polyshaped AuNPs synthesized with an aqueous macroalgae extract showed a satisfactory anticancer effect on the cell lines, as evaluated by changes in cell morphology, cell viability, and metabolic activity. An altered cellular function and the morphology of cancer cell lines suggest a potential for in vivo application of AuNPs and the need to understand the interactions between nanomaterials, biomolecules, and cellular components. With continued improvements, these NPs may prove to be potential drug delivery vehicles for cancer therapy., (© 2014 International Union of Biochemistry and Molecular Biology, Inc.)

Aim: The aim was to investigate antibacterial activity of Withania somnifera (Ashwagandha), an Indian traditional medicinal plant against Escherichia coli O78, a pathogenic strain., Materials and Methods: Two-fold serial dilutions of 20% aqueous W. somnifera root (WSR) extract were inoculated with E. coli O78 @ 1*10(7) colony forming units grown in nutrient broth. Following inoculation, turbidity optical density was measured by spectrophotometer at 600 nm in all the tubes at 0, 2, 4, 6 and 8 h of incubation at 37°C., Result: The results revealed that the maximum inhibition of bacterial growth was observed at 1:8 dilution of WSR extract. The highest dilution of the extract that showed inhibited growth of the test organism when compared with control was 1:16. Therefore, the minimum inhibitory concentration of aqueous extract of WSR is 1:16., Conclusion: It is concluded that WSR possessed good antibacterial activity, confirming the great potential of bioactive compounds and its rationalizing use in health care.

The present study has beenundertaken to evaluate the anti-inflammatory activity of two varieties of Pippali in acute and sub-acute experimental models of inflammation in albino rats. Four different market samples of each variety of Pippali were procured from different regions of India. The samples collected from South India which have given more extractive values were selected for screening of anti-inflammatory activity. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 200 mg/kg and the activity was compared with standard anti-inflammatory drugs in both models. Among the two different test samples studied, it was found that Chhoti variety of Pippali suppressed inflammation of both acute and sub acute phase, while Badi variety of Pippali only of acute phase. Thus for the therapeutic utility, Chhoti variety of Pippali may be considered over the Badi variety.

Increasing application of silver nanoparticles (SNPs) and zinc oxide nanoparticles (nZnO) in consumer products like textiles, cosmetics, washing machines and other household products increases their chance to reach the environment. Intensive research is required to assess the nanoparticles' toxicity to the environmental system. The toxicological effect of nanoparticles has been studied at the miniscule scale and requires intensive research to be conducted to assess its unknown effects. Plants are the primary target species which need to be included to develop a comprehensive toxicity profile for nanoparticles. So far, the mechanisms of toxicity of nanoparticles to the plant system remains largely unknown and little information on the potential uptake of nanoparticles by plants and their subsequent fate within the food chain is available. The phytoxicological behaviour of silver and zinc oxide nanoparticles on Allium cepa and seeds of Zea mays (maize), Cucumis sativus (cucumber) and Lycopersicum esculentum (tomato) was done. The in vitro studies on A. cepa have been done to check the cytotoxicological effects including mitotic index, chromosomal aberrations, vagrant chromosomes, sticky chromosomes, disturbed metaphase, breaks and formation of micronucleus. In vitro and in vivo studies on seed systems exposed to different concentration of nanoparticles dispersion to check phytotoxicity end point as root length, germination effect, adsorption and accumulation of nanoparticles (uptake studies) into the plant systems. In vivo studies in a seed system was done using phytagel medium. Biochemical studies were done to check effect on protein, DNA and thiobarbituric acid reactive species concentration. FT-IR studies were done to analyze the functional and conformational changes in the treated and untreated samples. The toxicological effects of nanoparticles had to be studied at the miniscule scale to address existing environment problems or prevent future problems. The findings suggest that the engineered nanoparticles, though having significant advantages in research and medical applications, requires a great deal of toxicity database to ascertain the biosafety and risk of using engineered nanoparticles in consumer products.

The aim of the present study was to investigate the potential of bioconversion of industrial herbal waste to vermicompost using Eudrilus eugeniae. Vermibeds were made using a mixture of herbal waste and cowdung (1 : 1) in comparison with the use of cowdung alone as substrate, resulting in vermicomposts 1 and 2, respectively. Different parameters were studied and it was observed that the nutrient profile of vermicompost 1 strongly influenced the growth of pea (Pisum sativum) and marigold plant (Tagetus erectus). The dry and fresh weight of shoots and roots, number of flowers, total yield in terms of fruit showed significant increase with vermicompost 1. Furthermore, vermicompost 1 (herbal waste and cow dung as substrate) resulted in a significant reduction in TOC by 58% in comparison with vermicompost 2 (cowdung as substrate). The C : N ratio was less than 20 in vermicompost 1 as well as in vermicompost 2, which indicated an advanced degree of stabilization and mineralization. The ability of earthworms to survive, grow and breed in the vermibed fed with the herbal waste indicates the sustainability and efficiency of a heterogeneous kind of organic waste. The results of the study suggested that bulk industrial herbal waste can be utilized as a substrate for vermicomposting and this can be proposed as an alternative for waste disposal in a clean green manner, promoting the concept of organic farming.

Increasing use of zinc oxide nanoparticles (ZnO NP) in consumer products may enhance its release into the environment. Phytotoxicity study is important to understand its possible environmental impact. Allium cepa (Onion bulb) is the best model organism to study genetic toxicology of nanoparticles. Here we have reported cytogenetic and genotoxic effects of ZnO NPs on the root cells of A. cepa. The effects of ZnO NPs on the mitotic index (MI), micronuclei index (MN index), chromosomal aberration index, and lipid peroxidation were determined through the hydroponic culturing of A. cepa. A. cepa roots were treated with the dispersions of ZnO NPs at four different concentrations (25, 50, 75, and 100 μg ml(-1)). With the increasing concentrations of ZnO NPs MI decreased with the increase of pycnotic cells, on the other hand MN and chromosomal aberration index increased. The frequency of micronucleated cells was higher in ZnO NPs treated cells as compared to control (deionized distilled water). The number of cells in each mitotic phase changed upon ZnO NPs treatment. The effect of ZnO NPs on lipid peroxidation as examined by measuring TBARS concentration was evident at all the concentrations compared to bulk ZnO. The TEM image showed internalization of ZnO NPs like particles. SEM image of treated A. cepa demonstrated that the internalized nanoparticles agglomerated depending on the physico-chemical environment inside the cell. Our results demonstrated that ZnO NPs can be a clastogenic/genotoxic and cytotoxic agent. In conclusion, the A. cepa cytogenetic test can be used for the genotoxicity monitoring of novel nanomaterials like ZnO NPs, which is used in many consumer products., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Potential health and environmental effects of nanoparticles need to be thoroughly assessed before their widespread commercialization. Though there are few studies on cytotoxicity of nanoparticles on mammalian and human cell lines, there are hardly any reports on genotoxic and cytotoxic behavior of nanoparticles in plant cells. This study aims to investigate cytotoxic and genotoxic impacts of silver nanoparticles using root tip cells of Allium cepa as an indicator organism. A.cepa root tip cells were treated with four different concentrations (25, 20, 75, and 100 ppm) of engineered silver nanoparticles (below 100 nm size) dispersion, to study endpoints like mitotic index, distribution of cells in mitotic phases, different types of chromosomal aberrations, disturbed metaphase, sticky chromosome, cell wall disintegration, and breaks. For each concentration five sets of microscopic observations were carried out. No chromosomal aberration was observed in the control (untreated onion root tips) and the mitotic index (MI) value was 60.3%. With increasing concentration of the nanoparticles decrease in the mitotic index was noticed (60.30% to 27.62%). The different cytological effects including the chromosomal aberrations were studied in detail for the treated cells as well as control. We infer from this study that silver nanoparticles could penetrate plant system and may impair stages of cell division causing chromatin bridge, stickiness, disturbed metaphase, multiple chromosomal breaks and cell disintegration. The findings also suggest that plants as an important component of the ecosystems need to be included when evaluating the overall toxicological impact of the nanoparticles in the environment.

Imatinib mesylate, a signal transduction inhibitor molecule, has been introduced in the treatment of chronic myelogenous leukemia (CML) since May 2001. By its unique mechanism of action, the drug has revolutionized the management of chronic phase CML. The drug is generally well tolerated. A number of hematological and non-hematological side-effects have been reported. Fatal bone marrow (BM) aplasia has rarely been reported. A 46-year-old women with chronic phase CML was treated with imatinib. Six weeks later she developed severe pancytopenia associated with fever, chest infection and bleeding. A BM biopsy revealed hypoplasia (BM cellularity < 5%). She died of pulmonary mucormycosis. CML patients on imatinib therapy need close monitoring. Those pre-treated with busulfan and interferon-alpha may be at a higher risk of developing BM aplasia.