Biodiesel production and exploring properties of Datura stramonium L. oil with its optimization using combined approaches-Taguchi, grey relational analysis, and response surface methodology.

Biodiesel production through the synthesis of Datura stramonium L. oil is studied to explore the most efficient approaches to suggest an alternate feedstock for biodiesel production. The main objective of this work is to optimize the process variables of biodiesel synthesis by using some statistical approach (Taguchi method, grey relational analysis (GRA), and response surface methodology (RSM) analyzing three parameters, i.e., alcohol-to-oil molar ratio, catalyst (NaOH) concentration, and process temperature for achieving maximum biodiesel derived from Datura stramonium L. oil. The transesterification process is applied by using an ultrasonic-assisted technique. Grey relational analysis (GRA) was successfully applied with the Taguchi method resulting in the optimum combination of A2B1C1. Based on the findings, the best operating conditions for transesterifying are attained with the RSM approach consisting of a 5.697:1 molar ratio (level 2), 0.3 (wt.%) NaOH concentration (level 1), and 70 °C process temperature (level 1). With a value of 87.02%, these ideal operating conditions produce the maximum yield as compared to grey relational analysis (GRA) yields 83.99%. The obtained results have been verified through the characterization of oil and biodiesel as well. Also, the fuel qualities of DSL biodiesel were identified and assessed. DSL oil was found 137.6 degrees of unsaturation during fatty acid profile analysis. DSL biodiesel was found the best kinematic viscosity (4.2 mm2/s) and acid value (0.49) when compared to Karanja and palm biodiesel. D. stramonium L. was recognized as a suitable species for biodiesel feedstock according to the findings.

Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.

Formulation of lactoferrin decorated dextran based chitosan-coated europium metal-organic framework for targeted delivery of curcumin.

Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic 'CS' on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of 'CUR' in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the 'CS' coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when 'Lf' is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting 'CUR' to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management.

Design of lactoferrin functionalized carboxymethyl dextran coated egg albumin nanoconjugate for targeted delivery of capsaicin: Spectroscopic and cytotoxicity studies.

The increased mortality rates associated with colorectal cancer highlight the pressing need for improving treatment approaches. While capsaicin (CAP) has shown promising anticancer activity, its efficacy is hampered due to low solubility, rapid metabolism, suboptimal bioavailability, and a short half-life. Therefore, this study aimed to prepare a lactoferrin-functionalized carboxymethyl dextran-coated egg albumin nanoconjugate (LF-CMD@CAP-EGA-NCs) for the targeted CAP delivery to enhance its potential for colorectal cancer therapy. Briefly, LF-CMD was synthesized through an esterification reaction involving LF as a receptor and CMD as a shell. Concurrently, CAP was incorporated into an EGA carrier using gelation and hydrophobic interactions. The subsequent production of LF-CMD@CAP-EGA-NCs was achieved through the Maillard reaction. Spectral characterizations confirmed the successful synthesis of smooth and spherical-shaped LF-CMD@CAP-EGA-NCs using LF-CMD and EGA-CAP nanoparticles, with high entrapment efficiency and satisfactory drug content. Furthermore, LF-CMD@CAP-EGA-NCs demonstrated a sustained release of CAP (76.52 ± 1.01 % in 24 h, R2 = 0.9966) in pH 5.8 buffer with anomalous transport (n = 0.68) owing to the shell of the CMD and EGA matrix. The nanoconjugate exhibited enhanced cytotoxicity in HCT116 and LoVo cell lines, which is attributed to the overexpression of LF receptors in colorectal HCT116 cells. Additionally, LF-CMD@CAP-EGA-NCs demonstrated excellent biocompatibility, as observed in the FHC-CRL-1831 cell line. In conclusion, LF-CMD@CAP-EGA-NCs can be considered as a promising approach for targeted delivery of CAP and other anticancer agents in colorectal cancer treatment.

Functionalized Graphene Quantum Dots (GQDs) based Label-Free Optical Fluorescence Sensor for CD59 Antigen Detection and Cellular Bioimaging.

Cluster of differentiation (CD59), a cell surface glycoprotein, regulates the complement system to prevent immune damage. In cancer, altered CD59 expression allows tumors to evade immune surveillance, promote growth, and resist certain immunotherapies. Targeting CD59 could enhance cancer treatment strategies by boosting the immune response against tumors. Herein, we present a one-step synthesis of Polyethyleneimine (PEI) functionalized graphene quantum dots (Lf-GQDs) from weathered lemon leaf extract. The fabricated Lf-GQDs were successfully used for the quantitative detection of the cluster of CD59 antigen that is reported for its expression in different types of cancer. In this work, we utilized orientation-based attachment of CD59 antibody (Anti-CD59). Our findings reveal that, instead of using random serial addition of antigen or antibody, oriented conjugation saves accumulated concentration offering greater sensitivity and selectivity. The Anti-CD59@Lf-GQDs immunosensor was fabricated using the oriented conjugation of antibodies onto the Lf-GQDs surface. Besides, the fabricated immunosensor demonstrated detection of CD59 in the range of 0.01 to 40.0 ng mL-1 with a low detection limit of 5.3 pg mL-1. Besides, the cellular uptake potential of the synthesized Lf-GQDs was also performed in A549 cells using a bioimaging study. The present approach represents the optimal utilization of Anti-CD59 and CD59 antigen. This approach could afford a pathway for constructing oriented conjugation of antibodies on the nanomaterials-based immunosensor for different biomarkers detection.

Stimuli-Responsive Design of Metal-Organic Frameworks for Cancer Theranostics: Current Challenges and Future Perspective.

Scientific fraternity revealed the potential of stimuli-responsive nanotherapeutics for cancer treatment that aids in tackling the major restrictions of traditionally reported drug delivery systems. Among stimuli-responsive inorganic nanomaterials, metal-organic frameworks (MOFs) have transpired as unique porous materials displaying resilient structures and diverse applications in cancer theranostics. Mainly, it demonstrates tailorable porosity, versatile chemical configuration, tunable size and shape, and feasible surface functionalization, etc. The present review provides insights into the design of stimuli-responsive multifunctional MOFs for targeted drug delivery and bioimaging for effective cancer therapy. Initially, the concept of cancer, traditional cancer treatment, background of MOFs, and approaches for MOFs synthesis have been discussed. After this, applications of stimuli-responsive multifunctional MOFs-assisted nanostructures that include pH, light, ions, temperature, magnetic, redox, ATP, and others for targeted drug delivery and bioimaging in cancer have been thoroughly discussed. As an outcome, the designed multifunctional MOFs showed an alteration in properties due to the exogenous and endogenous stimuli that are beneficial for drug release and bioimaging. The several reported types of stimuli-responsive surface-modified MOFs revealed good biocompatibility to normal cells, promising drug loading capability, target-specific delivery of anticancer drugs into cancerous cells, etc. Despite substantial progress in this field, certain crucial issues need to be addressed to reap the clinical benefits of multifunctional MOFs. Specifically, the toxicological compatibility and biodegradability of the building blocks of MOFs demand a thorough evaluation. Moreover, the investigation of sustainable and greener synthesis methods is of the utmost importance. Also, the low flexibility, off-target accumulation, and compromised pharmacokinetic profile of stimuli-responsive MOFs have attracted keen attention. In conclusion, the surface-modified nanosized design of inorganic diverse stimuli-sensitive MOFs demonstrated great potential for targeted drug delivery and bioimaging in different kinds of cancers. In the future, the preference for stimuli-triggered MOFs will open a new frontier for cancer theranostic applications.

Rhodamine 6G derivative for the selective copper detection and remediation using nanoporous diatomaceous earth-engineered functional receptor.

A rhodamine-derived receptor was synthesized and comprehensively characterized for structural confirmation. The receptor was able to distinguish the copper ions (Cu2+) from other competing cations. The yellow color of the receptor changed to pink upon adding Cu2+ ions, however, other competing cations ions were impotent towards any color variation. The UV-visible titration studies revealed the binding stoichiometry of a 1:1 ratio with a detection limit of 9.663 × 10-8 M. Additionally, a novel idea of the work resides in the use of diatom for the practical application, where the receptor has been tethered on nanoporous diatomaceous earth microparticles (P2D) to remove Cu2+ ions. The results confirmed that 50 mg receptor functionalized DE could adsorb 10 mL of 1 ppm Cu2+ ions from water. Furthermore, a proof-of-concept device that is inexpensive, simple to operate, and continuously removes Cu2+ ions from water has been developed. The efficiency of the device in Cu2+ ion removal could be realized through the naked eye by observing the color change of P2D particles, which has excellent potential for application in remote locations where water contamination is a significant issue.

Biosynthesis of Iron Oxide Nanoparticles Using Leaf Extract of Ruellia tuberosa: Mechanical and Dynamic Mechanical Behaviour Kevlar-Based Hybrid Epoxy Composites.

One of the more enticing, ecologically responsible, as well as safe and sustainable methodologies is eco-friendly nanomaterial synthesis. Vegetation materials will be used as reductants instead of toxic substances for synthesising nanoparticles. The current study used Ruellia tuberosa (RT) leaf extract digest to synthesise FeO nanomaterials, which were then characterised using XRD. Following that, microbially produced FeO molecules were mixed with a Kevlar-based polymeric matrix to study the blended consequences. To examine the interbreeding, the current experimental analyses were performed, including both static and dynamic mechanical characteristics. The addition of FeO nanofillers improved the elastic modulus, tensile strength, and storage modulus of the nanocomposite. Impact force uptake has been raised to a certain extent by the addition of nanoparticles. The findings of this research show that incorporating FeO nanofillers into Kevlar fabrics is a promising technique for increasing the mechanical characteristics of hybrid laminated composites. As per DMA evaluation, the sample without nanomaterials had a more volcanic lava response, which is a useful thing for body systems for missile use. Another critical aspect of a nanoparticles-filled nanocomposite that must be addressed is the relatively uniform scattering of padding as well as the development of interfacial adhesion in such a combination. The presence of FeO fillers in polymeric composites is confirmed by XRD analysis.

Awareness, perspectives and satisfaction levels among patients with psoriatic arthritis: a multicentric cross-sectional survey.

Perception of the disease and its management impacts patients with Psoriatic arthritis (PsA) to a great degree. Studies examining patients' viewpoints and perception of their disease and its management are scarce. This multicentric cross-sectional survey was undertaken to understand the perspectives of patients with PsA. A survey questionnaire with items on demographics, awareness about their disease, treatment, physical therapy, quality of life and satisfaction with the care received was designed. After internal and external validation, a pilot survey was conducted, and the questionnaire was finalized. The final survey (with translations in local languages) was carried out at 17 centres across India. There were 262 respondents (56% males) with mean age of 45.14 ± 12.89 years. In 40%, the time lag between onset of symptoms and medical assessment for it was more than a year. In most of the patients, the diagnosis of PsA was made by a rheumatologist. Over 83% of patients were consulting their rheumatologist periodically as advised and fully compliant with the treatment. Lack of time and cost of therapy were the most common reasons for non-adherence to therapy. Eighty-eight patients (34%) were not fully satisfied with their current treatment. Over two-third of patients had never seen a physiotherapist due to barriers including a lack of time, pain, and fatigue. The daily activities and employment status were affected in nearly 50% of patients with PsA. The current survey has identified a gap in patients' awareness levels and helps healthcare providers in understanding the varied perceptions of patients with PsA. Addressing these issues in a systematic manner would potentially improve the treatment approaches, outcomes, and patient satisfaction levels.

A unified multivariate statistical approach for the assessment of deep groundwater quality of rapidly growing city of Maharashtra Province, India, with potential health risk.

The main aim of this research is to assess the consequences of natural and anthropogenic processes on the groundwater quality of 65 deep aquifers of Nagpur city, Maharashtra Province, India, using a unified multivariate statistical approach. The dominant groundwater type recognized is Ca-HCO3 (recharge waters) in 43.1 and 38.5% of groundwater samples of pre- and post-monsoon seasons, followed by mixed water types. The seasonal distribution of physicochemical parameters shows increase in the concentration of EC, TDS, TH, Mg2+, SO42-, and NO3- signifying the high mineralization and anthropogenic loading from pre- and post-monsoon season respectively. The entropy-weight water quality index categorizes the 84.6% and 75.4% of total samples from pre- and post-monsoon seasons into moderate quality. The multiple linear regression and PCA analysis reveal the masking of rock weathering mechanism by anthropogenic activities. The % of PCA Variance varies from 79 to 83.7% from pre- to post-monsoon season. The high contributions of EC (0.76, 0.72), TDS (0.79, 0.73), TH (0.97, 0.962), Ca2+ (0.84, 0.78), Mg2+ (0.79, 0.83), Cl- (0.73, 0.75), and NO3- (0.78, 0.68) in PC1 components expose high salinity and hardness in urban groundwater that signifies the consequences of urbanization on the groundwater regime. About 55.4 and 70.8% of children population as compared to the adult female (53.8%, 69.2%) and male (32.3%, 46.1%) population in PRM and POM respectively were at high non-carcinogenic health threat of NO3--enriched groundwater. The study is beneficial for understanding the variation in groundwater composition due to unplanned urbanization and is very useful for protecting groundwater resources in urban areas.

Biofabricated functionalized graphene quantum dots (fGQDs): unraveling its fluorescence sensing mechanism of human telomerase reverse transcriptase (hTERT) antigen andin vitrobioimaging application.

Lung cancer (LC) is a deadly malignancy that is posing a serious threat to human health. Therefore, early detection of LC biomarkers is the key to reducing LC-related fatalities. Herein, we present the first fluorescent-based selective detection of LC biomarker human telomerase reverse transcriptase (hTERT) using polyethyleneimine (PEI) functionalized graphene quantum dots (fGQDs). One-potin situsynthesis of amine-functionalized GQDs was accomplished by hydrothermal carbonization of biowaste-derived cellulose and PEI. Synthesized fGQDs were characterized by various analytical techniques. Synthesized fGQDs not only exhibited enhanced fluorescence life-time but also excellent stability in the different solvents compared to bare GQDs. The surface activation of hTERT-Ab by carbodiimide chemistry (EDC-NHS) resulted in stacking interactions with fGQDs, involving adsorption-desorption as well as competitive mechanisms. The higher inherent affinity of hTERT-Ag (hTERT antigen) for hTERT-Ab (hTERT antibody) resulted in complex formation and recovery of fGQD fluorescence. As a result, this fluorescence sensing demonstrated a greater linear detection range (0.01 ng ml-1-100 µg ml-1) as well as a notable low detection limit (36.3 pg ml-1). Furthermore, the fabricated immunosensor (Ab@fGQDs) has excellent stability and performance in real samples, with an average recovery of 97.32%. The results of cytotoxicity and cellular bioimaging study in A549 cells show that fGQDs can be used for additional nanotherapeutics and biological applications.

Development of Novel Bio-mulberry-Reinforced Polyacrylonitrile (PAN) Fibre Organic Brake Friction Composite Materials.

Natural fibre reinforcement is used in important sectors such as medical, aerospace, automobile, and many other fields. Many articles have reported that natural fibre has the potential to replace synthetic fibres. Natural fibre reinforcement has given good results as a brake friction material. It has already been proven that asbestos causes lung cancer and mesothelioma in brakes. Many people died from the effects of asbestos. According to the World Health Organization's trending brake report, this material leads to serious health issues. This work is going on for the replacement of these materials. Mulberry fibre is a unique material, and PAN fibre is combined with mulberry fibre and used as a brake reinforcement material to replace Kevlar fibre. The brake pads were fabricated with the various wt% of mulberry fibres and PAN fibre [3-12%] with an equal ratio and aramid fibre [3-6%] in the hydraulic hind brake moulding machine. The mechanical, chemical, physical, tribological, and thermal properties were evaluated. MF-2 [6 wt%] mulberry-PAN-fibre-based brake pad composites have shown better results for ultimate shear strength and proof stress, tensile strength, compressive strength, and impact energy.

Role of Curcumin in Reducing Toxicities Associated With Mucosal Injury Following Melphalan-Based Conditioning in Autologous Transplant Setting.

Mucositis is nearly inevitable following high-dose chemotherapy. Several pro-inflammatory cytokines play a role in pathogenesis of mucositis. Curcumin inhibits inflammatory cytokines through inhibition of nuclear factor kappa-ß. We studied the effects of curcumin on the acute toxicities and inflammatory cytokines following melphalan (200 mg/m2) for autologous hematopoietic stem cell transplantation (HSCT) for myeloma. The control group (first 10 enrolled patients who received standard supportive care) was compared with curcumin group (next 30 patients who received chewable curcumin lozenges, 4 g twice daily from 2 days before melphalan till day +28 along with standard supportive care). The toxicities were recorded as per World Health Organization (WHO) criteria and CTCAE v3.0 as applicable. Cytokine profiling was done in both groups at similar time points. In the curcumin group, there was significant decrease in grade 3/4 vomiting (3% vs 40%, P = 0.01) and total parenteral nutrition use (47% vs 90%, P = 0.026). Grade 3/4 mucositis (43% vs 60%) and diarrhea (33% vs 70%) were also less, but not statistically significant. This coincided with 3.2-fold lower area under the concentration time curve (AUC) of IL-8 from day -3 to day 14 in curcumin group compared with control group (P = 0.039). We conclude that curcumin mitigates toxicities of high-dose melphalan, possibly through IL-8 modulation. Randomized studies are warranted to explore benefits of curcumin in HSCT.

Fabrication of Poly-l-lysine-Functionalized Graphene Quantum Dots for the Label-Free Fluorescent-Based Detection of Carcinoembryonic Antigen.

The diagnosis of tumor biomarkers is an attentive approach for the early detection and treatment of cancer. However, a cost-effective, simple, rapid, selective, and sensitive method is a basic prerequisite for diagnostic research. Herein, we present a novel fluorescence-based label-free sensing strategy for the sensitive and selective detection of carcinoembryonic antigen (CEA) using poly-l-lysine (PLL)-functionalized graphene quantum dots (GQDs). The GQDs were synthesized using a greener method by employing carbonized peanut shell (PNS) waste as a carbon source, and functionalization was accomplished using PLL (PLL-GQDs). The fluorescence stability of the PLL-GQDs was tested in a variety of solvent systems and pH solutions. When compared to nonfunctionalized GQDs (PNS-GQDs), prepared PLL-GQDs demonstrated increased fluorescence lifetime, high quantum yield, excellent photostability, biocompatibility, and greater cellular uptake. The PLL-GQDs with abundant surface amine and carboxylic groups showed selective interactions with an activated CEA antibody (CEA-Ab), resulting in the quenching of fluorescence signals. Because of the strong bioaffinity of CEA to the CEA-Ab, the antibody was unwrapped, resulting in the formation of an antibody-antigen complex and the recovery of fluorescence. As a result of this relationship, a turn "on-off-on" sensing mechanism with a strong response to CEA concentration (0.01 ng mL-1 to 100 µg mL-1) and a detection limit of 1.19 pg mL-1 was demonstrated. Furthermore, the fabricated CEA immunosensor (CEA-Ab@PLL-GQDs) performed admirably in real sample analysis, with an average recovery of 98.32%. The cellular uptake performance of PLL-GQDs was also demonstrated in the A427 cell lines, exhibiting a greater cellular uptake potential than PNS-GQDs. The cellular bioimaging study demonstrates that PLL-GQDs can be used for additional therapeutic and biological applications.

Graphene quantum dots (GQDs) nanoarchitectonics for theranostic application in lung cancer.

Lung cancer (LC) is heading up as a substantial cause of mortality worldwide. Despite enormous progress in cancer management, LC remains a crucial problem for oncologists due to the lack of early diagnosis and precise treatment. In this context, numerous early diagnosis and treatment approaches for LC at the cellular level have been developed using advanced nanomaterials in the last decades. Amongst this, graphene quantum dots (GQDs) as a novel fluorescent material overwhelmed the horizons of materials science and biomedical fields due to their multifunctional attributes. Considering the complex nature of LC, emerging diagnostic and therapeutic (Theranostics) strategies using GQDs proved to be an effective way for the current practice in LC. In this line, we have abridged various approaches used in the LC theranostics using GQDs and its surface-engineered motif. The admirable photophysical attributes of GQDs realised in photolytic therapy (PLT), hyperthermia therapy (HTT), and drug delivery have been discussed. Furthermore, we have engrossed the impasse and its effects on the use of GQDs in cancer treatments from cellular level (in vivo-in vitro) to clinical. Inclusively, this review will be an embodiment for the scientific fraternity to design and magnify their view for the theranostic application of GQDs in LC treatment.

Combining High-Throughput Synthesis and High-Throughput Protein Crystallography for Accelerated Hit Identification.

Protein crystallography (PX) is widely used to drive advanced stages of drug optimization or to discover medicinal chemistry starting points by fragment soaking. However, recent progress in PX could allow for a more integrated role into early drug discovery. Here, we demonstrate for the first time the interplay of high throughput synthesis and high throughput PX. We describe a practical multicomponent reaction approach to acrylamides and -esters from diverse building blocks suitable for mmol scale synthesis on 96-well format and on a high-throughput nanoscale format in a highly automated fashion. High-throughput PX of our libraries efficiently yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent, SARS-CoV-2. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT PX has the potential to accelerate hit finding and to provide meaningful strategies for medicinal chemistry projects.

Effects of N-terminus modified Hx-amides on DNA binding affinity, sequence specificity, cellular uptake, and gene expression.

Five X-HxIP (Hx-amides) 6a-e, in which the N-terminus p-anisyl moiety is modified, were designed and synthesised with the purpose of optimising DNA binding, improving cellular uptake/nuclear penetration, and enhancing the modulation of the topoisomerase IIα (TOP2A) gene expression. The modifications include a fluorophenyl group and other heterocycles bearing different molecular shapes, size, and polarity. Like their parent compound HxIP 3, all five X-HxIP analogues bind preferentially to their cognate sequence 5'-TACGAT-3', which is found embedded on the 5' flank of the inverted CCAAT box-2 (ICB2) site in the TOP2A gene promoter, and inhibit protein complex binding. Interestingly, the 4-pyridyl analog 6a exhibits greater binding affinity for the target DNA sequence and abolishes the protein:ICB2 interaction in vitro, at a lower concentration, compared to the prototypical compound HxIP 3. Analogues 6b-e, display improved DNA sequence specificity, but reduced binding affinity for the cognate sequence, relative to the unmodified HxIP 3, with polyamides 6b and 6e being the most sequence selective. However, unlike 3 and 6b, 6a was unable to enter cells, access the nucleus and thereby affect TOP2A gene expression in confluent human lung cancer cells. These results show that while DNA binding affinity and sequence selectivity are important, consideration of cellular uptake and concentration in the nucleus are critical when exerting biological activity is the desired outcome. By characterising the DNA binding, cellular uptake and gene regulatory properties of these small molecules, we can elucidate the determinants of the elicited biological activity, which can be impacted by even small structural modifications in the polyamide molecular design.

Design and evaluation of hyaluronic acid-coated PLGA nanoparticles of raloxifene hydrochloride for treatment of breast cancer.

CONTEXT: In the present study, hyaluronic acid (HA)-coated raloxifene-loaded poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles have been developed to improve the anticancer potential and reduce side effects associated with the drug. AIM AND OBJECTIVES: The investigation was aimed to formulate and optimize raloxifene hydrochloride (RALH)-loaded PLGA nanoparticles with surface modification using HA as a targeting moiety. To perform physicochemical characterization, in vitro cytotoxicity study (using MCF-7), in vitro drug release study and in vivo pharmacodynamic study of optimized formulation. METHODOLOGY: Raloxifene hydrochloride-loaded PLGA nanoparticles were prepared by nanoprecipitation technique, followed by surface modification with HA. Formulation was optimized by using 23 factorial design and characterized by physicochemical, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics. RESULTS AND DISCUSSION: The particle size, PDI, zeta potential, entrapment efficiency, and loading capacity of spherically shaped RALH-loaded nanoparticles were 207.3 ± 4.2 d.nm, 0.218 ± 0.127, -.127 mV, 43.75 ± 1.2%, and 7.55 ± 1.14%, respectively. The in vitro drug release showed sustained release and followed Korsmeyer-Peppas model with non-Fickian release pattern. The in vitro cytotoxicity study of drug-loaded NPs by MTT assay on MCF-7 breast carcinoma cell showed anti-cancer activity after 48 h of treatment. CONCLUSION: The results of the present investigation suggested that RALH-loaded HA-modified PLGA nanoparticles showed sustained drug release with anticancer activity and can be a promising approach for treatment of breast cancer.

Black Phosphorus as Multifaceted Advanced Material Nanoplatforms for Potential Biomedical Applications.

Black phosphorus is one of the emerging members of two-dimensional (2D) materials which has recently entered the biomedical field. Its anisotropic properties and infrared bandgap have enabled researchers to discover its applicability in several fields including optoelectronics, 3D printing, bioimaging, and others. Characterization techniques such as Raman spectroscopy have revealed the structural information of Black phosphorus (BP) along with its fundamental properties, such as the behavior of its photons and electrons. The present review provides an overview of synthetic approaches and properties of BP, in addition to a detailed discussion about various types of surface modifications available for overcoming the stability-related drawbacks and for imparting targeting ability to synthesized nanoplatforms. The review further gives an overview of multiple characterization techniques such as spectroscopic, thermal, optical, and electron microscopic techniques for providing an insight into its fundamental properties. These characterization techniques are not only important for the analysis of the synthesized BP but also play a vital role in assessing the doping as well as the structural integrity of BP-based nanocomposites. The potential role of BP and BP-based nanocomposites for biomedical applications specifically, in the fields of drug delivery, 3D printing, and wound dressing, have been discussed in detail to provide an insight into the multifunctional role of BP-based nanoplatforms for the management of various diseases, including cancer therapy. The review further sheds light on the role of BP-based 2D platforms such as BP nanosheets along with BP-based 0D platforms-i.e., BP quantum dots in the field of therapy and bioimaging of cancer using techniques such as photoacoustic imaging and fluorescence imaging. Although the review inculcates the multimodal therapeutic as well as imaging role of BP, there is still research going on in this field which will help in the development of BP-based theranostic platforms not only for cancer therapy, but various other diseases.

Caval Valve Implantation for Tricuspid Regurgitation: Insights From the United States Caval Valve Registry.

BACKGROUND: We sought to describe the outcomes of patients who underwent caval valve implantation (CAVI) for treatment of severe tricuspid regurgitation (TR) in the United States. Previous studies on CAVI have used a variety of techniques and transcatheter valves. We present our findings from CAVI with inferior vena cava (IVC) implant only using a single valve. METHODS: Patients who were determined to be poor candidates for tricuspid valve surgery and underwent CAVI in the United States from March 1, 2013 through March 1, 2018 were included in this study. Data during hospitalizations and interim outpatient follow-up from each individual site were collected and entered into a central password-protected database. RESULTS: A total of 24 patients were treated. The median age was 79.5 years, 63% were women, and 96% were white. Twenty-three of 24 patients underwent valve implantation with a 29 mm Sapien 3 valve (Edwards Lifesciences). There was a 100% rate of successful valve implantation. There were no cases requiring emergency surgery. Thirty-day mortality rate was 25%. The median survival as of last follow-up of all patients was 350 days. Pre- and postprocedure New York Heart Association (NYHA) class data were available in 11 of 24 patients; of these 11 patients, 72.7% improved at least 1 NYHA class from baseline. CONCLUSION: CAVI may be performed safely in a high surgical risk population with severe tricuspid regurgitation. Dedicated studies with longer-term follow-up are needed.