An Updated Review Summarizing the Anticancer Potential of Poly(Lactic-co-Glycolic Acid) (PLGA) Based Curcumin, Epigallocatechin Gallate, and Resveratrol Nanocarriers.

The utilization of nanoformulations derived from natural products for the treatment of many human diseases, including cancer, is a rapidly developing field. Conventional therapies used for cancer treatment have limited efficacy and a greater number of adverse effects. Hence, it is imperative to develop innovative anticancer drugs with superior effectiveness. Among the diverse array of natural anticancer compounds, resveratrol, curcumin, and epigallocatechin gallate (EGCG) have gained considerable attention in recent years. Despite their strong anticancer properties, medicinally significant phytochemicals such as resveratrol, curcumin, and EGCG have certain disadvantages, such as limited solubility in water, stability, and bioavailability problems. Encapsulating these phytochemicals in poly(lactic-co-glycolic acid) (PLGA), a polymer that is nontoxic, biodegradable, and biocompatible, is an effective method for delivering medication to the tumor location. In addition, PLGA nanoparticles can be modified with targeting molecules to specifically target cancer cells, thereby improving the effectiveness of phytochemicals in fighting tumors. Combining plant-based medicine (phytotherapy) with nanotechnology in a clinical environment has the potential to enhance the effectiveness of drugs and improve the overall health outcomes of patients. Therefore, it is crucial to have a comprehensive understanding of the different aspects and recent advancements in using PLGA-based nanocarriers for delivering anticancer phytochemicals. This review addresses the most recent advancements in PLGA-based delivery systems for resveratrol, EGCG, and curcumin, emphasizing the possibility of resolving issues related to the therapeutic efficacy and bioavailability of these compounds.

Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents.

Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -ß.

Waste derived modified biochar as promising functional material for enhanced water remediation potential.

The waste management and water purification are daunting environmental challenges. Biochar, a carbonaceous material prepared from diverse organic waste (agricultural, household residues and municipal sewage sludge) has garnered substantial attention due to its excellent attributes, including carbon content, cation exchange efficacy, ample specific surface area, and structural robustness. Thus, the present review comprehensively analyzes bio waste-derived biochar with a particular emphasis on water remediation applications. This article primarily delves into various strategies for modifying biochar, elucidating the underlying mechanisms behind these modifications and their potential for bolstering pollutant removal efficiency. Furthermore, it addresses the impact of functionalization on both biochar stability and cost for commercialization. Lastly, the article outlines key developments, SWOT analysis, and future prospects, offering insights into the practical execution of biochar applications at a larger scale. Therefore, this article paves the way for future research to deepen the understanding of modified biochar with mechanisms for exploring water remediation applications in a more sustainable manner.

Recent advances in waste-derived carbon dots and their nanocomposites for environmental remediation and biological applications.

The surging demand for eco-friendly nanomaterial synthesis has spurred the emergence of green approaches for synthesizing carbon dots (CDs). These methods utilized natural carbon sources, such as different kind of waste for CDs synthesis, underscoring their significance in waste management and circular economy initiatives. Furthermore, the properties of CDs can be tailored by their functionalization with different materials, enabling their versatile utilization in diverse scientific domains. In this regard, the current study delves into an in-depth review of recent advances in the green/sustainable fabrication of carbon dots nanocomposites (CDNCs) with metal/metal oxides and polymers within the timeframe of 2019-2023. It begins by categorizing different types of CDs, analyzing their associated nanocomposites with mechanistic insights. The primary focus is on green synthesis methods, particularly those that employ waste materials. Furthermore, we also discussed the applications of these CDs in both environmental and biological fields by covering areas such as catalysis, photocatalysis, heavy metal ion sensing, antimicrobial, and bioimaging with in-depth underlying mechanisms. At last, the review highlights the significant challenges with future directions. These include the pursuit of cost-effective green precursors, the advancement of streamlined one-step synthesis techniques, and their efficient utilization for diverse applications. Therefore, this review provides valuable insights for researchers seeking to enhance the functionality and sustainability of CDNCs by highlighting their potential to address environmental and biological challenges.

Exploring the abundance of microplastics in Indian landfill leachate: An analytical study.

Landfills are a major source of many emerging pollutants, including microplastics (MPs). This makes them a potential threat to human and environmental health and calls for a more detailed analysis of their hazard potential. India is a developing country with multiple unscientific waste dumping sites. In spite of their hazardous nature, detailed studies on the abundance of microplastics in landfills in India are scanty. Current work investigates the abundance and diversity of MPs in two landfills of India, Uruli Devachi in Pune (S1) and Deonar in Mumbai (S2). MPs collected from landfill leachate using multiple filters were analyzed using an optical microscope and categorized on the basis of shape, color and size to give information on their distribution. MP abundance in S1 was 1473 ± 273.01 items/L while 2067 ± 593.75 items/L were found in leachate from S2. Film and fragment were the dominant shape and black was the dominant color of MP found in both the landfills. Maximum number of MPs were in the size range below 100 µm in both the landfills necessitating the study of small sized particles. Chemical characterization revealed the prevalence of four types of MPs (polyethylene terephthalate, polypropylene, cellulose acetate and polyvinyl chloride). This study sheds light on the prevalence, characteristics, abundance and distribution of MPs in landfill leachate in Western India, sparking more research into the processes followed for capturing the factual small sized microplastic abundance data. This study is vital for a detailed management of landfill leachate enabling a sustainable waste management and targeted actions for ecosystem preservation.

Interaction Patterns of Pyrazolopyrimidines with Receptor Proteins.

Heterocyclic compounds have a prominent role in medicinal chemistry and drug design. They are not only useful as medicinally active compounds but also as a modular structural scaffold for drug design. Therefore, heterocycles are present in many ligands that exhibit a broad spectrum of biological activities. Pyazolopyrimidines are nitrogen heterocycles and are part of many biologically active compounds and marketed drugs. This study examines the non-covalent interactions between the pyrazolopyrimidine rings and receptor proteins through data mining and analysis of high-resolution crystal structures deposited in the Protein Data Bank. The Protein Data Bank contains 471 crystal structures with pyrazolopyrimidine derivatives as ligands, among which 50% contains 1H-pyrazolo[3,4-d]pyrimidines (Pyp1), while 38% contains pyrazolo[1,5-a] pyrimidines (Pyp2). 1H-Pyrazolo[4,3-d]pyrimidines (Pyp3) are found in 11% of the structures, and no structural data is available for pyrazolo[1,5-c]pyrimidine isomers (Pyp4). Among receptor proteins, transferases are found in most examples (67.5%), followed by hydrolases (13.4%) and oxidoreductases (8.9%). Detailed analysis of structures to identify the most prevalent interactions of pyrazolopyrimidines with proteins shows that aromatic π···π interactions are present in ∼91% of the structures and hydrogen bonds/other polar contacts are present in ∼73% of the structures. The centroid-centroid distances (dcent) between the pyrazolopyrimidine rings and aromatic side chains of the proteins have been retrieved from crystal structures recorded at a high resolution (data resolution <2.0 Å). The average value of dcent in pyrazolopyrimidine-protein complexes is 5.32 Å. The information on the geometric parameters of aromatic interactions between the core pyrazolopyrimidine ring and the protein would be helpful in future in silico modeling studies on pyrazolopyrimidine-receptor complexes.

Biogenic silver based nanostructures: Synthesis, mechanistic approach and biological applications.

The alarming impact of antibiotic resistance sparked the quest for complementary treatments to overcome the confrontation over resistant pathogens. Metallic nanoparticles, especially silver nanoparticles (Ag NPs) have gained a much attention because of their remarkable biological characteristics. Moreover, their medicinal properties can be enhanced by preparing the composites with other materials. This article delves a comprehensive review of biosynthesis route for Ag NPs and their nanocomposites (NCs) with in-depth mechanism, methods and favorable experimental parameters. Comprehensive biological features Ag NPs such as antibacterial, antiviral, antifungal have been examined, with a focus on their potential uses in biomedicine and diagnostics has also been discussed. Additionally, we have also explored the hitches and potential outcomes of biosynthesis of Ag NPs in biomedical filed.

Tuning of (E)-(4-fluorophenyl)-1,1-diamino-2,3-diazabuta-1,3-diene nanostructures for the selective detection of imidacloprid.

The present work demonstrates a facile route for synthesizing the organic nanoparticles (ONPs) and the blue fluorescent Quantum Dots (QDs) based on an organic molecule named (E)-(4-fluorophenyl)-1,1-diamino-2,3-diazabuta-1,3-diene. The synthesis process possesses advantages viz green synthesis, non-toxic degraded products, and amount of organic compound. Initially, the ONPs were prepared using the nanoprecipitation method and were screened for their recognition potential against various pesticides, however, no selectivity has been observed. This motivated us to tune the ONPs into QDs. The QDs were prepared using the hydrothermal method and a color change was observed in the QDs solution under daylight and under a UV lamp. The emission wavelength was observed at 400 nm (λexcitation = 278 nm). The synthesized QDs exhibited selective sensing potential towards imidacloprid via a quenching mechanism. A normalised decrement in the luminescence intensity of QDs was observed on raising the concentration of imidacloprid and a good linear response was noticed over a concentration varies from 1 µM to 100 µM with a regression coefficient of 0.99. The detection limit was estimated to be 4.53 nM and quantification limit was calculated to be and 13.72 nM.

Potential medicinal plants to combat viral infections: A way forward to environmental biotechnology.

The viral diseases encouraged scientific community to evaluate the natural antiviral bioactive components rather than protease inhibitors, harmful organic molecules or nucleic acid analogues. For this purpose, medicinal plants have been gaining tremendous importance in the field of attenuating the various kinds of infectious and non-infectious diseases. Most of the commonly used medicines contains the bioactive components/phytoconstituents that are generally extracted from medicinal plants. Moreover, the medicinal plants offer many advantages for the recovery applications of infectious disease especially in viral infections including HIV-1, HIV-2, Enterovirus, Japanese Encephalitis Virus, Hepatitis B virus, Herpes Virus, Respiratory syncytial virus, Chandipura virus and Influenza A/H1N1. Considering the lack of acceptable drug candidates and the growing antimicrobial resistance to existing drug molecules for many emerging viral diseases, medicinal plants may offer best platform to develop sustainable/efficient/economic alternatives against viral infections. In this regard, for exploring and analyzing large volume of scientific data, bibliometric analysis was done using VOS Viewer shedding light on the emerging areas in the field of medicinal plants and their antiviral activity. This review covers most of the plant species that have some novel bioactive compound like gnidicin, gniditrin, rutin, apigenin, quercetin, kaempferol, curcumin, tannin and oleuropin which showed high efficacy to inhibit the several disease causing virus and their mechanism of action in HIV, Covid-19, HBV and RSV were discussed. Moreover, it also delves the in-depth mechanism of medicinal with challenges and future prospective. Therefore, this work delves the key role of environment in the biological field.

Suicide and Suicidality in Children and Adolescents with Chronic Skin Disorders: A Systematic Review.

Suicide in young children is rare; the incidence increases towards the end of adolescence. Skin disorders confer a high prevalence of psychiatric and psycho-logical comorbidities. However, published research on suicidal behaviour in adolescents and children with skin disorders is sparse. The aim of this study was to identify the prevalence of suicidal behaviour in children and adolescents under 18 years of age with chronic skin disorders and associated contributing risk factors. MEDLINE, PsycINFO, EMBASE, CINAHL and Cochrane databases were searched from inception to October 2020 for suicide or suicide attempts in patients under 18 years old with chronic skin disorders. The study protocol was logged on PROSPERO (CRD42020083528). Returned texts were reviewed independently by 2 authors. Bias was assessed according to Joanna Briggs Institute criteria. Five studies met the inclusion criteria; 4 cross-sectional surveys and 1 retrospective matched-cohort study. A total of 31,641 patients with acne, atopic dermatitis, body dysmorphic disorder or psoriasis were identified. Prevalence of suicidal ideation was 0.45% (psoriasis) to 67% (body dysmorphic disorder). The prevalence of suicidal attempts ranged from 0.08% (psoriasis) to 21.9% (acne). Patients with acne or atopic dermatitis had significantly increased odds ratio for suicidal attempts. Meta-analysis could not be performed owing to the heterogeneity and sparsity of data. Suicidal risk in skin disorders amongst adolescents and children under the age of 18 years old is broad and complex. The suicidal risk remained after adjusting for depression, suggestive of an alternative mechanism.

Elucidating the Molecular Structure of Hydrophobically Modified Polyethylenimine Nanoparticles and Its Potential Implications for DNA Binding.

The structural properties of the polyethylenimine (PEI) polymer are generally tuned and selectively modified to reinforce its potential in a broad spectrum of applied domains of medicine, healthcare, material design, sensing, and electronic optimization. The selective modification of the polymer brings about changes in its interfacial characteristics and behavior. The current work involves the synthesis of naphthalimide conjugated polyethylenimine organic nanoparticles (NPEI-ONPs). The interfacial molecular structure of NPEI-ONPs is explored in an aqueous medium at pH 7.4 using surface tensiometry and sum-frequency generation vibrational spectroscopy (SFG-VS). The hydrophobic functionalization rendered a concentration-dependent surface coverage of NPEI-ONPs, where the SFG-VS analysis exhibited the molecular rearrangement of its hydrophobic groups at the interface. The interaction of NPEI-ONPs with double-stranded DNA (dsDNA) is carried out to observe the relevance of the synthesized nanocomposites in the biomedical domain. The bulk-specific studies (i.e., thermal denaturation, viscometry, zeta (ζ) potential, and ATR-FTIR) reveal the condensation of dsDNA in the presence of NPEI-ONPs, making its structure more compact. The interface-sensitive SFG-VS showcased the impact of the dsDNA and NPEI-ONP interaction on the interfacial molecular behavior of NPEI-ONPs at the air-aqueous interface. Our results exhibit the potential of such hydrophobically functionalized ONPs as promising candidates for developing biomedical sealants, substrate coatings, and other biomedical domains.

Mechanistic investigation of formation of highly-dispersed silver nanoparticles using sea buckthorn extract.

Nowadays, the greener pathways for the synthesis of nanostructures are being explored. The extracts of different parts of plantsvizleaves, stems, and roots have been investigated. However, these extracts have been prepared by simply boiling or microwaving, or sonicating the parts of plants with water. Therefore, to have deeper insight and to investigate the full potential of plant extracts, serial extraction of leaves of sea buckthorn (Hippophae rhamnoides L.) which is a medicinally important plant was attempted using the soxhlet apparatus. The as-obtained polyphenolic-rich extract was employed for the preparation of silver nanoparticles (Ag-NPs). Under optimized reaction conditionsviz60 °C temperature and 500µl of extract solution (5 mg ml-1) highly disperse spherical nanoparticles of the average size of 15.8 ± 4.8 nm were obtained. Further, the optical band gap of Ag-NPs prepared using optimized reaction conditions was found to be 2.6 eV using the Tauc equation. Additionally, to understand the reduction by the extract, kinetic studies were also carried out which suggest the predominant occurrence of pseudo-first-order reaction. Furthermore, the mechanism of formation of Ag-NPs using major components of extractvizgallic acid and catechin which were identified by HPLC were also investigated using DFT. The mechanistic investigation was performed for both the keto-enol and radical-mediated preparation of Ag-NPs. Such theoretical investigations will help in the efficient designing of greener and novel routes for the synthesis of Ag-NPs. Additionally, the prepared silver was also employed for the colorimetric detection of H2O2.

IL@CQD catalyzed active ester rearrangement for the detection and removal of cyanide ions.

Carbon Quantum Dots (CQDs) have been extensively employed in various fields of science such as sensing, catalysis, and drug delivery. In this work, ionic liquid coated CQDs (IL@CQDs) have been used as catalysts for the rearrangement of a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) amide coupling intermediate. The rearranged product was confirmed by single crystal structure analysis and it was processed into organic nanoparticles (ONPs). An optical detection method was used to scrutinize the anion sensing properties. The ONPs were found to be sensitive and selective for the recognition of highly toxic cyanide ions through enhancement in the fluorescence intensity. The cyanide ion co-ordinates with the -NH groups of the product and restricts the rotation of molecules around the single bond. The ONPs coated over silica-beads were also showing CN- recognition in the solid state. The detection limit for CN- sensing was found to be 3.8 nM, and real sample analysis depicts more than 90% accuracy in detection.

Naphthalimide-Based DNA-Coupled Hybrid Assembly for Sensing Dipicolinic Acid: A Biomarker for Bacillus anthracis Spores.

We have designed and synthesized a novel, water-soluble naphthalimide-histidine receptor (1) with excellent fluorescent properties. Functioning of the synthesized receptor was performed through developing their DNA-receptor hybrid assembly (DRHA), which has shown significant changes in the emission profile upon interactions with dipicolinic acid (DPA), a biomarker for Bacillus anthracis spores. DRHA showed fluorescence enhancement upon binding with DPA with the characteristic of internal charge transfer. It is notable that this assembly exhibited a significant limit of detection (12 nM) toward DPA. The mechanism of sensing was fully defined using ethidium bromide (EtBr) interaction studies as well as Fourier transform infrared spectroscopic analysis, which describes the binding mode of DRHA with DPA. This assembly selectively interacts with DPA over other anions, common cellular cations, and aromatic acids in aqueous media.

Regulatory T-cell neutralization in mice during filariasis helps in parasite clearance by enhancing T helper type 17-mediated pro-inflammatory response.

Lymphatic filariasis leads to profound impairment of parasite-specific T helper type 1 (Th1) and Th2 immune responses and significantly increases the expression of regulatory networks and regulatory effectors like transforming growth factor-ß, CD25, cytotoxic T-lymphocyte antigen 4, glucocorticoid-induced tumour necrosis factor receptor (GITR) and regulatory T (Treg) cells, which together play an important role in immunosuppression. While Treg cells suppress the activity of effector cells, monocyte dysfunction, characterized by an alternatively activated immunoregulatory phenotype, is one hypothesis that explains the lack of an antigen-specific T-cell response in infected individuals. In the present study, we administered neutralizing antibodies against the Treg cell-associated markers CD25 and GITR and observed its effects on filaria-induced immunosuppression. Our results show that administration of anti-CD25 and anti-GITR in infected animals not only arrested the accumulation of Treg cells and reduced arginase activity, but also led to an increase in the percentages of Th17 cells in the secondary lymphoid organs of mice. Elevated levels of interferon-γ and decreased levels of interleukin-10 were also noted in the culture supernatants of mouse splenocytes that were treated with neutralizing antibodies. Furthermore, treatment with neutralizing antibodies enhanced the expression of inducible nitric oxide synthase on host macrophages and CD40 on host dendritic cells with concomitant decreased expression of alternative activation markers Arg1, Ym1 and Fizz1, which together lead to reduced parasite burden in treated animals. In summary, administration of neutralizing antibodies helps in breaking the regulatory network in mice and limits parasite-induced immunosuppression at the earliest host-parasite interface.

Wolbachia endosymbiont of Brugia malayi elicits a T helper type 17-mediated pro-inflammatory immune response through Wolbachia surface protein.

Wolbachia is an endosymbiotic bacterium of the filarial nematode Brugia malayi. The symbiotic relationship between Wolbachia and its filarial host is dependent on interactions between the proteins of both organisms. However, little is known about Wolbachia proteins that are involved in the inflammatory pathology of the host during lymphatic filariasis. In the present study, we cloned, expressed and purified Wolbachia surface protein (r-wsp) from Wolbachia and administered it to mice, either alone or in combination with infective larvae of B. malayi (Bm-L3) and monitored the developing immune response in infected animals. Our results show that spleens and mesenteric lymph nodes of mice immunized with either r-wsp or infected with Bm-L3 show increased percentages of CD4(+) T helper type 17 (Th17) cells and Th1 cytokines like interferon-γ and interleukin-2 (IL-2) along with decreased percentages of regulatory T cells, Th2 cytokines like IL-4 and IL-10 and transforming growth factor ß (TGF-ß) levels in culture supernatants of splenocytes. These observations were stronger in mice immunized with r-wsp alone. Interestingly, when mice were first immunized with r-wsp and subsequently infected with Bm-L3, percentages of CD4(+) Th17 cells and Th1 cytokines increased even further while that of regulatory T cells, Th2 cytokines and TGF-ß levels decreased. These results for the first time show that r-wsp acts synergistically with Bm-L3 in promoting a pro-inflammatory response by increasing Th17 cells and at the same time diminishes host immunological tolerance by decreasing regulatory T cells and TGF-ß secretion.

Barium ferrite decorated reduced graphene oxide nanocomposite for effective electromagnetic interference shielding.

There is an increased interest in the development of high performance microwave shielding materials against electromagnetic pollution in recent years. Barium ferrite decorated reduced graphene oxide (BaFe12O19@RGO) nanocomposite was synthesized by a high energy ball milling technique and its electromagnetic properties were investigated in the frequency range of 12.4-18 GHz (Ku band). The results showed that barium ferrite (BaFe12O19) nanoparticles with an average particle size of 20-30 nm were well distributed and firmly anchored onto the surface of the reduced graphene oxide sheets. The obtained nanocomposite exhibited a saturation magnetization of 18.1 emu g(-1) at room temperature. The presence of BaFe12O19 nanoparticles in the nanocomposite enhances the space charge polarization, natural resonance, multiple scattering and the effective anisotropy energy leading to a high electromagnetic interference shielding effectiveness of 32 dB (∼99.9% attenuation) at a critical thickness of 3 mm. The results suggested that the as-prepared BaFe12O19@RGO nanocomposite showed great potential as an effective candidate for a new type of microwave absorbing material.

Impact of single immunosuppressive drug withdrawal on lymphocyte immunoreactivity.

BACKGROUND: Chronic rejection is a major cause of graft loss in kidney transplant recipients. Nonadherence to drug therapy is a well-recognized cause of chronic rejection leading to long-term graft dysfunction and failure for transplant recipients. Immunosuppressive medications with short half-lives that require frequent dosing, such as tacrolimus, complicate transplant regimens and may increase noncompliance. Regimens could be simplified using drugs with long half-lives requiring once-daily administration, such as sirolimus. The impact of missing doses of single agents has not been studied extensively. Erratic compliance or temporary discontinuation of immunosuppressive drugs may have significant implications for chronic rejection. METHODS: Our study evaluated the impact of single drug withdrawal of commonly used immunosuppressive agents (sirolimus and tacrolimus) on lymphocyte responses. We analyzed lymphocyte proliferation, cytokine secretion, and adenosine triphosphate generation using a crossover study design with normal healthy patients. Lymphocyte proliferation was assessed using 5-bromo-2-deoxyuridine incorporation, and T cell function was analyzed by examining adenosine triphosphate generation. RESULTS: Our results indicate that sirolimus exerts prolonged suppression of lymphocyte proliferation and decreased interleukin 17A that lasts up to 48 h after drug withdrawal. In comparison, tacrolimus did not have a similar effect on lymphocyte proliferation or interleukin 17A secretion. CONCLUSION: Future analysis of sirolimus in diverse transplantation populations merits investigation.