Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Biogenic nanoparticles: pioneering a new era in breast cancer therapeutics-a comprehensive review.

Breast cancer, a widespread malignancy affecting women globally, often arises from mutations in estrogen/progesterone receptors. Conventional treatments like surgery, radiotherapy, and chemotherapy face limitations such as low efficacy and adverse effects. However, nanotechnology offers promise with its unique attributes like targeted delivery and controlled drug release. Yet, challenges like poor size distribution and environmental concerns exist. Biogenic nanotechnology, using natural materials or living cells, is gaining traction for its safety and efficacy in cancer treatment. Biogenic nanoparticles synthesized from plant extracts offer a sustainable and eco-friendly approach, demonstrating significant toxicity against breast cancer cells while sparing healthy ones. They surpass traditional drugs, providing benefits like biocompatibility and targeted delivery. Thus, this current review summarizes the available knowledge on breast cancer (its types, stages, histopathology, symptoms, etiology and epidemiology) with the importance of using biogenic nanomaterials as a new and improved therapy. The novelty of this work lies in its comprehensive examination of the challenges and strategies for advancing the industrial utilization of biogenic metal and metal oxide NPs. Additionally; it underscores the potential of plant-mediated synthesis of biogenic NPs as effective therapies for breast cancer, detailing their mechanisms of action, advantages, and areas for further research.

Combination chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model.

The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood-brain-barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood-brain-barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs + P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6% of the NPs were concentrated in the brain after 48 h. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.

Dietary Minerals and Incident Cardiovascular Outcomes among Never-Smokers in a Danish Case-Cohort Study.

Background: Diet is known to impact cardiovascular disease (CVD) risk, but evidence for the essential minerals of magnesium (Mg), calcium (Ca), and potassium (K) is inconsistent. Methods: We conducted a case-cohort study within a non-smoking subgroup of the Danish Diet, Cancer and Health cohort, a prospective study of 50-64-year-olds recruited between 1993-1997. We identified incident heart failure (HF), acute myocardial infarction (AMI) and stroke cases through 2015 with an 1135-member subcohort. We measured the dietary intake of minerals, also known as elements, and calculated a combined dietary intake (CDI) score based on joint Ca, Mg and K intakes (mg/d) from Food Frequency Questionnaires. We estimated adjusted hazard ratios (HRs) with Cox proportional hazard models. Results: Most HRs examining associations between CDI score and CVD were null. However, the third quartile of CDI was associated with a lower risk for heart failure (HR: 0.89; 95% CI: 0.67, 1.17), AMI (HR: 0.79; 95% CI: 0.60, 1.04), and stroke (HR: 0.63; 95% CI: 0.44, 0.88). Conclusions: We did not find consistent evidence to suggest that higher levels of essential minerals are associated with incident HF, AMI, and stroke, though results suggest a potential U-shaped relationship between select minerals and CVD outcomes.

High Strength and Shape Memory Spinal Fusion Device for Minimally Invasive Interbody Fusions.

Introduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation. Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement. Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa. Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.

Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity.

Periodontal disease is a multifactorial pathogenic condition involving microbial infection, inflammation, and various systemic complications. Here, a systematic and comprehensive review discussing key-points such as the pros and cons of conventional methods, new advancements, challenges, patents and products, and future prospects is presented. A systematic review process was adopted here by using the following keywords: periodontal diseases, pathogenesis, models, patents, challenges, recent developments, and 3-D printing scaffolds. Search engines used were "google scholar", "web of science", "scopus", and "pubmed", along with textbooks published over the last few decades. A thorough study of the published data rendered an accurate and deep understanding of periodontal diseases, the gap of research so far, and future opportunities. Formulation scientists and doctors need to be interconnected for a better understanding of the disease to prescribe a quality product. Moreover, prime challenges (such as a lack of a vital testing model, scarcity of clinical and preclinical data, products allowing for high drug access to deeper tissue regions for prolonged residence, lack of an international monitoring body, lack of 4D or time controlled scaffolds, and lack of successful AI based tools) exist that must be addressed for designing new quality products. Generally, several products have been commercialized to treat periodontal diseases with certain limitations. Various strategic approaches have been attempted to target certain delivery regions, maximize residence time, improve efficacy, and reduce toxicity. Conclusively, the current review summarizes valuable information for researchers and healthcare professional to treat a wide range of periodontal diseases.

Children's exposure to brominated flame retardants in the home: The TESIE study.

Due to differences in chemical properties and half-lives, best practices for exposure assessment may differ for legacy versus novel brominated flame retardants (BFRs). Our objective was to identify the environment matrix that best predicted biomarkers of children's BFR exposures. Paired samples were collected from children aged 3-6 years and their homes, including dust, a small piece of polyurethane foam from the furniture, and a handwipe and wristband from each child. Biological samples collected included serum, which was analyzed for 11 polybrominated diphenyl ethers (PBDEs), and urine, which was analyzed for tetrabromobenzoic acid (TBBA), a metabolite of 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB). Significant positive correlations were typically observed between BFRs measured in dust, handwipes and wristbands, though wristbands and handwipes tended to be more strongly correlated with one another than with dust. PBDEs, EH-TBB and BEH-TEBP were detected in 30% of the sofa foam samples, suggesting that the foam was treated with PentaBDE or Firemaster® 550/600 (FM 550/600). PBDEs were detected in all serum samples and TBBA was detected in 43% of urine samples. Statistically significant positive correlations were observed between the environmental samples and serum for PBDEs. Urinary TBBA was 6.86 and 6.58 times more likely to be detected among children in the highest tertile of EH-TBB exposure for handwipes and wristbands, respectively (95 % CI: 2.61, 18.06 and 1.43, 30.05 with p < 0.001 and 0.02, respectively). The presence of either PentaBDE or FM 550/600 in furniture was also associated with significantly higher levels of these chemicals in dust, handwipes and serum (for PBDEs) and more frequent detection of TBBA in urine (p = 0.13). Our results suggest that children are exposed to a range of BFRs in the home, some of which likely originate from residential furniture, and that silicone wristbands are a practical tool for evaluating external exposure to both legacy and novel BFRs.

Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms.

There is an increasing demand for innovative strategies that effectively promote osteogenesis and enhance bone regeneration. The critical process of bone regeneration involves the transformation of mesenchymal stromal cells into osteoblasts and the subsequent mineralization of the extracellular matrix, making up the complex mechanism of osteogenesis. Icariin's diverse pharmacological properties, such as anti-inflammatory, anti-oxidant, and osteogenic effects, have attracted considerable attention in biomedical research. Icariin, known for its ability to stimulate bone formation, has been found to encourage the transformation of mesenchymal stromal cells into osteoblasts and improve the subsequent process of mineralization. Several studies have demonstrated the osteogenic effects of icariin, which can be attributed to its hormone-like function. It has been found to induce the expression of BMP-2 and BMP-4 mRNAs in osteoblasts and significantly upregulate Osx at low doses. Additionally, icariin promotes bone formation by stimulating the expression of pre-osteoblastic genes like Osx, RUNX2, and collagen type I. However, icariin needs to be effectively delivered to bone to perform such promising functions.Encapsulating icariin within nanoplatforms holds significant promise for promoting osteogenesis and bone regeneration through a range of intricate biological effects. When encapsulated in nanofibers or nanoparticles, icariin exerts its effects directly at the cellular level. Recalling that inflammation is a critical factor influencing bone regeneration, icariin's anti-inflammatory effects can be harnessed and amplified when encapsulated in nanoplatforms. Also, while cell adhesion and cell migration are pivotal stages of tissue regeneration, icariin-loaded nanoplatforms contribute to these processes by providing a supportive matrix for cellular attachment and movement. This review comprehensively discusses icariin-loaded nanoplatforms used for bone regeneration and osteogenesis, further presenting where the field needs to go before icariin can be used clinically.

Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity.

Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance partly through a dysbiotic gut microbiota and changes in the serum levels of secondary bile acids (BAs). Serum BAs, per- and polyfluoroalkyl substances (PFAS) and additional twenty-seven ETs were measured by mass spectrometry in 264 Danes (121 men and 143 women, aged 56.6 ± 7.3 years, BMI 29.7 ± 6.0 kg/m2) using a combination of targeted and suspect screening approaches. Bacterial species were identified based on whole-genome shotgun sequencing (WGS) of DNA extracted from stool samples. Personalized genome-scale metabolic models (GEMs) of gut microbial communities were developed to elucidate regulation of BA pathways. Subsequently, we compared findings from the human study with metabolic implications of exposure to perfluorooctanoic acid (PFOA) in PPARα-humanized mice. Serum levels of twelve ETs were associated with obesity and insulin resistance. High chemical exposure was associated with increased abundance of several bacterial species (spp.) of genus (Anaerotruncus, Alistipes, Bacteroides, Bifidobacterium, Clostridium, Dorea, Eubacterium, Escherichia, Prevotella, Ruminococcus, Roseburia, Subdoligranulum, and Veillonella), particularly in men. Conversely, females in the higher exposure group, showed a decrease abundance of Prevotella copri. High concentrations of ETs were correlated with increased levels of secondary BAs including lithocholic acid (LCA), and decreased levels of ursodeoxycholic acid (UDCA). In silico causal inference analyses suggested that microbiome-derived secondary BAs may act as mediators between ETs and obesity or insulin resistance. Furthermore, these findings were substantiated by the outcome of the murine exposure study. Our combined epidemiological and mechanistic studies suggest that multiple ETs may play a role in the etiology of obesity and insulin resistance. These effects may arise from disruptions in the microbial biosynthesis of secondary BAs.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Establishment of the mechanism of purification and levigation of green chemistry-assisted biocomposites of red ochre (Gairika): synthesis, characterization, and antibacterial, prebiotic, antioxidant, and antacid activities of the traditional Ayurvedic medicine Laghu Sutashekhara Rasa.

Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5-8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow's butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.

Agrowaste-generated biochar for the sustainable remediation of refractory pollutants.

The rapid growth of various industries has led to a significant, alarming increase in recalcitrant pollutants in the environment. Hazardous dyes, heavy metals, pesticides, pharmaceutical products, and other associated polycyclic aromatic hydrocarbons (such as acenaphthene, fluorene, fluoranthene, phenanthrene, and pyrene) have posed a significant threat to the surroundings due to their refractory nature. Although activated carbon has been reported to be an adsorbent for removing contaminants from wastewater, it has its limitations. Hence, this review provides an elaborate account of converting agricultural waste into biochar with nanotextured surfaces that can serve as low-cost adsorbents with promising pollutant-removing properties. A detailed mechanism rationalized that this strategy involves the conversion of agrowaste to promising adsorbents that can be reduced, reused, and recycled. The potential of biowaste-derived biochar can be exploited for developing biofuel for renewable energy and also for improving soil fertility. This strategy can provide a solution to control greenhouse gas emissions by preventing the open burning of agricultural residues in fields. Furthermore, this serves a dual purpose for environmental remediation as well as effective management of agricultural waste rich in both organic and inorganic components that are generated during various agricultural operations. In this manner, this review provides recent advances in the use of agrowaste-generated biochar for cleaning the environment.

How to fix a broken heart-designing biofunctional cues for effective, environmentally-friendly cardiac tissue engineering.

Cardiovascular diseases bear strong socioeconomic and ecological impact on the worldwide healthcare system. A large consumption of goods, use of polymer-based cardiovascular biomaterials, and long hospitalization times add up to an extensive carbon footprint on the environment often turning out to be ineffective at healing such cardiovascular diseases. On the other hand, cardiac cell toxicity is among the most severe but common side effect of drugs used to treat numerous diseases from COVID-19 to diabetes, often resulting in the withdrawal of such pharmaceuticals from the market. Currently, most patients that have suffered from cardiovascular disease will never fully recover. All of these factors further contribute to the extensive negative toll pharmaceutical, biotechnological, and biomedical companies have on the environment. Hence, there is a dire need to develop new environmentally-friendly strategies that on the one hand would promise cardiac tissue regeneration after damage and on the other hand would offer solutions for the fast screening of drugs to ensure that they do not cause cardiovascular toxicity. Importantly, both require one thing-a mature, functioning cardiac tissue that can be fabricated in a fast, reliable, and repeatable manner from environmentally friendly biomaterials in the lab. This is not an easy task to complete as numerous approaches have been undertaken, separately and combined, to achieve it. This review gathers such strategies and provides insights into which succeed or fail and what is needed for the field of environmentally-friendly cardiac tissue engineering to prosper.

Anticancer and antibacterial properties of carbon nanotubes are governed by their functional groups.

Due to their high strength, low weight, and biologically-inspired dimensions, carbon nanotubes have found wide interest across all of medicine. In this study, four types of highly dispersible multi-walled carbon nanotubes (CNTs) of similar dimensions, but slightly different chemical compositions, were compared with an unmodified material to verify the impact their surface chemistry has on cytocompatibility, anticancer, inflammation, and antibacterial properties. Minute changes in the chemical composition were found to greatly affect the biological performance of the CNTs. Specifically, the CNTs with a large number of carbon atoms with a +2 coordination number induced cytotoxicity in macrophages and melanoma cells, and had a moderate antibacterial effect against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria strains, all while being cytocompatible towards human dermal fibroblasts. Moreover, substituting some of the OH groups with ammonia diminished their cytotoxicity towards macrophages while still maintaining the aforementioned positive qualities. At the same time, CNTs with a large number of carbon atoms with a +3 coordination number had a high innate cytocompatibility towards normal healthy cells but were toxic towards cancer cells and bacteria. The latter was further boosted by reacting the CNTs' carboxyl groups with ammonia. Although requiring further analyses, the results of this study, thus, introduce new CNTs that without drugs can treat cancer, inflammation, and/or infection while still remaining cytocompatible with mammalian cells.

The food and biomedical applications of curcumin-loaded electrospun nanofibers: A comprehensive review.

Encapsulating curcumin (CUR) in nanocarriers such as liposomes, polymeric micelles, silica nanoparticles, protein-based nanocarriers, solid lipid nanoparticles, and nanocrystals could be efficient for a variety of industrial and biomedical applications. Nanofibers containing CUR represent a stable polymer-drug carrier with excellent surface-to-volume ratios for loading and cell interactions, tailored porosity for controlled CUR release, and diverse properties that fit the requirements for numerous applications. Despite the mentioned benefits, electrospinning is not capable of producing fibers from multiple polymers and biopolymers, and the product's effectiveness might be affected by various machine- and material-dependent parameters like the voltage and the flow rate of the electrospinning process. This review delves into the current and innovative recent research on nanofibers containing CUR and their various applications.

Quantification of Phytochemicals and Metal Ions as well as the Determination of Volatile Compounds, Antioxidant, Antimicrobial and Antacid Activities of the Mimosa pudica L. Leaf: Exploration of Neglected and Under-Utilized Part.

Mimosa pudica L. (MP) is well-known plant in traditional medicinal system, especially in India. Unfortunately, leaves of MP are less explored. To determine the food and nutritional value of the neglected part of Mimosa pudica L. (MP), that is MP leaves, phytochemicals and metal ions of MP were quantified by newly developed HPLC and ICPOES-based methods. The content of phytochemicals observed using HPLC analysis for chlorogenic acid, catechin, and epicatechin was 141.823 (±8.171), 666.621 (±11.432), and 293.175 (±12.743) µg/g, respectively. Using GC/MS/MS analysis, fatty acid like oleic acid were identified. In ICP-OES analysis, a significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The observed TPC and TFC for MP leaf extracts was 44.327 (±1.041) mg GAE/ g of wt. and 214.217 (±4.372) mg QCE/ g of wt., respectively. The DPPH assay depicted a strong antioxidant activity of MP leaf extracts with IC50 values of 0.796 (±0.081) mg/mL and a TEAC value of 0.0356 (±0.0003). A significant antacid activity (666 mg MP+400 mg CaCO3 >400 mg CaCO3 ≫666 mg Gelusil) of MP leaves was noticed. The methanolic extract of MP leaves demonstrated anti-microbial activity against Staphylococcus aureus (15±2mm), Pseudomonas aeruginosa (12±2mm) and Escherichia coli (10±2mm). In silico studies confirmed the in vitro results obtained for antioxidant, antiacid, and anti-microbial activities. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the MP leaves. In summary, this study demonstrated the medicinal significance of MP leaves and the conversion of agro-waste or the under-utilized part of MP into pharmaceutical potent materials. Consequently, the present study highlighted that MP leaves alone have medicinal importance with good nutritional utility and possess large promise in the pharma industry along with improving bio-valorization and the environment.

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

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

Biogenic nanoparticles from waste fruit peels: Synthesis, applications, challenges and future perspectives.

Nanotechnology is a continually growing field with a wide range of applications from food science to biotechnology and nanobiotechnology. As the current world is grappling with non-biodegradable waste, considered more challenging and expensive to dispose of than biodegradable waste, new technologies are needed today more than ever. Modern technologies, especially nanotechnology, can transform biodegradable waste into products for human use. Researchers are exploring sustainable pathways for nanotechnology by utilizing biodegradable waste as a source for preparing nanomaterials. Over the past ten years, the biogenic production of metallic nanoparticles (NPs) has become a promising alternative technique to traditional NPs synthesis due to its simplicity, eco-friendliness, and biocompatibility in nature. Fruit and vegetable waste (after industrial processing) contain various bioactives (such as flavonoids, phenols, tannins, steroids, triterpenoids, glycosides, anthocyanins, carotenoids, ellagitannins, vitamin C, and essential oils) serving as reducing and capping agents for NP synthesis and they possess antibacterial, antioxidant, and anti-inflammatory properties. This review addresses various sources of biogenic NPs including their synthesis using fruit/vegetable waste, types of biogenic NPs, extraction processes and extracted biomaterials, the pharmacological functionality of NPs, industrial aspects, and future perspectives. In this manner, this review will cover the most recent research on the biogenic synthesis of NPs from fruit/vegetable peels to transform them into therapeutic nanomedicines.

Unknown Organofluorine Mixtures in U.S. Adult Serum:Contribution from Pharmaceuticals?

Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: -1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS.