Discovery of novel 6-(piperidin-1-ylsulfonyl)-2H-chromenes targeting α-glucosidase, α-amylase, and PPAR-γ: Design, synthesis, virtual screening, and anti-diabetic activity for type 2 diabetes mellitus.

A new series of 2H-chromene-based sulfonamide derivatives 3-12 has been synthesized and characterized using different spectroscopic techniques. The synthesized 2H-chromenes were synthesized by reacting activated methylene with 5-(piperidin-1-ylsulfonyl)salicylaldehyde through one-step condensation followed by intramolecular cyclization. Virtual screening of the designed molecules on α-glucosidase enzymes (PDB: 3W37 and 3A4A) exhibited good binding affinity suggesting that these derivatives may be potential α-glucosidase inhibitors. In-vitro α-glucosidase activity was conducted firstly at 100 µg/mL, and the results demonstrated good inhibitory potency with values ranging from 90.6% to 96.3% compared to IP = 95.8% for Acarbose. Furthermore, the IC50 values were determined, and the designed derivatives exhibited inhibitory potency less than 11 µg/mL. Surprisingly, two chromene derivatives 6 and 10 showed the highest potency with IC50 values of 0.975 ± 0.04 and 0.584 ± 0.02 µg/mL, respectively, compared to Acarbose (IC50 = 0.805 ± 0.03 µg/mL). Moreover, our work was extended to evaluate the in-vitro α-amylase and PPAR-γ activity as additional targets for diabetic activity. The results exhibited moderate activity on α-amylase and potency as PPAR-γ agonist making it a multiplet antidiabetic target. The most active 2H-chromenes 6 and 10 exhibited significant activity to PPAR-γ with IC50 values of 3.453 ± 0.14 and 4.653 ± 0.04 µg/mL compared to Pioglitazone (IC50 = 4.884±0.29 µg/mL) indicating that these derivatives improve insulin sensitivity by stimulating the production of small insulin-sensitive adipocytes. In-silico ADME profile analysis indicated compliance with Lipinski's and Veber's rules with excellent oral bioavailability properties. Finally, the docking simulation was conducted to explain the expected binding mode and binding affinity.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 µg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 µM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 µM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 µg mL-1, compared to Acarbose (0.604 ± 0.02 µg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 µg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 µg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Cananga odorata (Ylang-Ylang) Essential Oil Containing Nanoemulgel for the Topical Treatment of Scalp Psoriasis and Dandruff.

This research aimed to evaluate the efficacy of a nanoemulgel (NE) containing Cananga odorata (Ylang-Ylang) oil for managing scalp psoriasis and dandruff through various assessments. The study involved phytochemical screening, characterization, stability testing, in vivo performance evaluation, dermatokinetic analysis, central composite rotatable design (CCRD) optimization, in vitro release profiling, and antioxidant and antimicrobial activity assessment of the NE. The NE exhibited excellent stability and maintained physical parameters over a three-month period. In vivo studies showed no skin irritation, maintenance of skin pH (4.55 to 5.08), and improvement in skin hydration (18.09 to 41.28 AU) and sebum content (26.75 to 5.67 mg/cm2). Dermatokinetic analysis revealed higher skin retention of C. odorata in the NE (epidermis: 71.266 µg/cm2, dermis: 60.179 µg/cm2) compared to conventional formulations. CCRD optimization yielded NE formulations with the desired particle size (195.64 nm), entrapment efficiency (85.51%), and zeta potential (-20.59 mV). In vitro release studies indicated sustained release behavior, and antioxidant and antimicrobial properties were observed. This study demonstrates the stability, skin-friendliness, therapeutic benefits, and controlled release properties of the NE. The NE presents a promising option for various topical applications in treating bacterial and fungal diseases, potentially enhancing drug delivery and treatment outcomes in pharmaceuticals and cosmetics.

Recent Advances in Carbon Nanotube Utilization in Perovskite Solar Cells: A Review.

Due to their exceptional optoelectronic properties, halide perovskites have emerged as prominent materials for the light-absorbing layer in various optoelectronic devices. However, to increase device performance for wider adoption, it is essential to find innovative solutions. One promising solution is incorporating carbon nanotubes (CNTs), which have shown remarkable versatility and efficacy. In these devices, CNTs serve multiple functions, including providing conducting substrates and electrodes and improving charge extraction and transport. The next iteration of photovoltaic devices, metal halide perovskite solar cells (PSCs), holds immense promise. Despite significant progress, achieving optimal efficiency, stability, and affordability simultaneously remains a challenge, and overcoming these obstacles requires the development of novel materials known as CNTs, which, owing to their remarkable electrical, optical, and mechanical properties, have garnered considerable attention as potential materials for highly efficient PSCs. Incorporating CNTs into perovskite solar cells offers versatility, enabling improvements in device performance and longevity while catering to diverse applications. This article provides an in-depth exploration of recent advancements in carbon nanotube technology and its integration into perovskite solar cells, serving as transparent conductive electrodes, charge transporters, interlayers, hole-transporting materials, and back electrodes. Additionally, we highlighted key challenges and offered insights for future enhancements in perovskite solar cells leveraging CNTs.

LncRNAs: Emerging biomarkers and therapeutic targets in rectal cancer.

According to findings, long non-coding RNAs (lncRNAs) have an important function in the onset and growth of various cancers, including rectal cancer (RC). RC offers unique issues in terms of diagnosis, treatment, and results, needing a full understanding of the cellular mechanisms that cause it to develop. This thorough study digs into the various functions that lncRNAs perform in RC, giving views into their multiple roles as well as possible therapeutic consequences. The function of lncRNAs in RC cell proliferation, apoptosis, migratory and infiltrating capacities, epithelial-mesenchymal shift, and therapy tolerance are discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell functions such as angiogenesis, death, immunity, and growth. Systemic lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. Besides adding to their diagnostic utility, lncRNAs offer therapeutic opportunities as actors, contributing to the expanding landscape of cancer research. Moreover, the investigation looks into the assessment and predictive utility of lncRNAs as RC markers. The article also offers insight into lncRNAs as chemoresistance and drug resistance facilitators in the setting of RC.

Beyond the genome: MALAT1's role in advancing urologic cancer care.

Urologic cancers (UCs), which include bladder, kidney, and prostate tumors, account for almost a quarter of all malignancies. Long non-coding RNAs (lncRNAs) are tissue-specific RNAs that influence cell growth, death, and division. LncRNAs are dysregulated in UCs, and their abnormal expression may allow them to be used in cancer detection, outlook, and therapy. With the identification of several novel lncRNAs and significant exploration of their functions in various illnesses, particularly cancer, the study of lncRNAs has evolved into a new obsession. MALAT1 is a flexible tumor regulator implicated in an array of biological activities and disorders, resulting in an important research issue. MALAT1 appears as a hotspot, having been linked to the dysregulation of cell communication, and is intimately linked to cancer genesis, advancement, and response to treatment. MALAT1 additionally operates as a competitive endogenous RNA, binding to microRNAs and resuming downstream mRNA transcription and operation. This regulatory system influences cell growth, apoptosis, motility, penetration, and cell cycle pausing. MALAT1's evaluation and prognosis significance are highlighted, with a thorough review of its manifestation levels in several UC situations and its association with clinicopathological markers. The investigation highlights MALAT1's adaptability as a possible treatment target, providing fresh ways for therapy in UCs as we integrate existing information The article not only gathers current knowledge on MALAT1's activities but also lays the groundwork for revolutionary advances in the treatment of UCs.

Hydrothermally Synthesized Z-Scheme Nanocomposite of ZIF-9 Modified MXene for Photocatalytic Degradation of 4-Chlorophenol.

4-Chlorophenol (4CP) is a well-known environmental contaminant often detected in wastewater, generally arising from industrial processes such as chemical manufacture, pharmaceutical production, and pesticide formulation. 4CP is a matter of great concern since it is persistent and has the potential to have harmful impacts on both aquatic ecosystems and human health, owing to its hazardous and mutagenic properties. Hence, degradation of 4CP is of utmost significance. This research investigates the photocatalytic degradation of 4CP using a novel Z-scheme heterojunction nanocomposite composed of MXene and ZIF-9. The nanocomposite is synthesized through a two-step hydrothermal method and thoroughly characterized by using XRD, SEM, UV-visible spectroscopy, zeta potential, and electrochemical impedance spectroscopy studies, confirming successful fabrication with improved surface properties. The comparative photocatalytic degradation studies between pristine materials and the nanocomposite were performed, and significant enhancement in performance was observed. The effect of pH on the degradation efficiency is also explored and correlated with the surface charge. The Z-scheme photocatalysis mechanism is proposed, which is supported by time-resolved photoluminescence studies and scavenger experiments. The reusability of the nanocomposite is also evaluated. The study contributes to the development of efficient and sustainable photocatalysts for wastewater treatment.

Overcoming chemoresistance and radio resistance in prostate cancer: The emergent role of non-coding RNAs.

Prostate cancer (PCa) continues to be a major health concern worldwide, with its resistance to chemotherapy and radiation therapy presenting major hurdles in successful treatment. While patients with localized prostate cancer generally have a good survival rate, those with metastatic prostate cancer often face a grim prognosis, even with aggressive treatments using various methods. The high mortality rate in severe cases is largely due to the lack of treatment options that can offer lasting results, especially considering the significant genetic diversity found in tumors at the genomic level. This comprehensive review examines the intricate molecular mechanisms governing resistance in PCa, emphasising the pivotal contributions of non-coding RNAs (ncRNAs). We delve into the diverse roles of microRNAs, long ncRNAs, and other non-coding elements as critical regulators of key cellular processes involved in CR & RR. The review emphasizes the diagnostic potential of ncRNAs as predictive biomarkers for treatment response, offering insights into patient stratification and personalized therapeutic approaches. Additionally, we explore the therapeutic implications of targeting ncRNAs to overcome CR & RR, highlighting innovative strategies to restore treatment sensitivity. By synthesizing current knowledge, this review not only provides a comprehension of the chemical basis of resistance in PCa but also identifies gaps in knowledge, paving the way for future research directions. Ultimately, this exploration of ncRNA perspectives offers a roadmap for advancing precision medicine in PCa, potentially transforming therapeutic paradigms and improving outcomes for patients facing the challenges of treatment resistance.

Genetic variants associated with dengue hemorrhagic fever. A systematic review and meta-analysis.

Dengue hemorrhagic fever (DHF) is a severe condition resulting from the dengue virus, with four serotypes known as DEN-1, DEN-2, DEN-3, and DEN-4. Genetic variations play a crucial role in influencing susceptibility to DHF. Therefore, this investigation conducted a meta-analysis to uncover genetic changes that might have remained undetected in individual studies due to small sample sizes or methodological differences. Among 2212 initially identified studies, 23 were deemed suitable for analysis based on PRISMA guidelines. Toll-like receptors (TLR) and CD209 showed significant association with DHF (odds ratios: TLR=0.56, CD209 =0.55), indicating protective effects. However, tumor necrosis factor (TNF) and human leukocyte antigen (HLA) did not exhibit a statistically significant relationship with DHF. This study emphasizes the relevance of TLR and CD209 in DHF susceptibility and resistance across diverse geographical locations.

A comprehensive review on the applications of ferrite nanoparticles in the diagnosis and treatment of breast cancer.

Various conventional treatments including endocrine therapy, radiotherapy, surgery, and chemotherapy have been used for several decades to treat breast cancer; however, these therapies exhibit various life-threatening and debilitating adverse effects in patients. Additionally, combination therapies are required for prompt action as well as to prevent drug resistance toward standard breast cancer medications. Ferrite nanoparticles (NPs) are increasingly gaining momentum for their application in the diagnosis and treatment of breast cancer. Spinel ferrites are particularly used against breast cancer and have shown in vitro and in vivo better efficacy as compared to conventional cancer therapies. Magnetic resonance imaging contrast agents, magnetic particle imaging tracers, cell separation, and immune assays are some aspects related to the diagnosis of breast cancer against which different ferrite NPs have been successfully evaluated. Moreover, citrate-coated nickel ferrite, Mg/Zn ferrites, poly amidoamine dendrimers, cobalt ferrites, graphene oxide cobalt ferrites, doxorubicin functionalized cobalt ferrites, chitosan-coated zinc ferrites, PEG-coated cobalt ferrite, and copper ferrite NPs have demonstrated antiproliferative action against different breast cancer cells. Oxaliplatin-loaded polydopamine/BSA-copper ferrites, functionalized cobalt and zinc ferrites of curcumin, oxaliplatin-copper ferrite NPs, tamoxifen/diosgenin encapsulated ZnO/Mn ferrites, and fabricated core-shell fibers of doxorubicin have been developed to increase the bioavailability and anti-proliferative effect and decrease the toxicity of anticancer drugs. These ferrite NPs showed an anticancer effect at different doses in the presence or absence of an external magnetic field. The present review covers the in-depth investigations of ferrite NPs for the diagnosis and management of breast cancer.

Investigation of natural compounds as methyltransferase inhibitors against dengue virus: an in silico approach.

The global challenge posed by Dengue virus (DENV) infection persists, exacerbated by the absence of specific antiviral therapies. The viral methyltransferase (MTase) enzyme, crucial for viral RNA methylation and immune system evasion, has emerged as a promising drug target for combating Dengue fever. In this study, a comprehensive exploration of natural compounds derived from the COCONUT database was conducted, selecting 224 compounds based on their structural similarity to the native substrate of the MTase enzyme, S-adenosyl-L-methionine (SAM). Employing virtual screening techniques, four natural compounds (CNP0307160, CNP0082902, CNP0449158, and CNP0296775) with acceptable docking scores were selected for further re-docking after geometry optimization by the DFT method. Re-docking analyses unveiled significant interactions, including hydrogen bonds and hydrophobic interactions, between these selected ligands and the MTase protein. To gain deeper insights into the dynamic stability of these complexes, we conducted molecular dynamics simulations which showed lower RMSD values for CNP0307160, CNP0082902, and CNP0296775 when compared to the reference molecule. Furthermore, we assessed the structural and dynamic stability of the protein-ligand complexes through free binding energy calculations and Principal Component Analysis (PCA) of the simulation trajectories. In these analyses, the CNP0296775 compound exhibited promising results compared to the other three compounds. The cumulative findings of these investigations underscore the potential of CNP0296775 as a strong inhibitor of DENV MTase, thus offering a promising starting point for its further experimental validation and optimization.Communicated by Ramaswamy H. Sarma.

Chitosan Nanoparticles for Enhanced Delivery of Sida cordifolia Extract: Formulation, Optimization and Bioactivity Assessment.

In a continuous search for an essential antidiabetic agent, Sida cordifolia hydroalcoholic (SCHA) extract-loaded chitosan nanoparticles (SCHA-CS-NP) were optimized. The Box-Behnken design (BBD Design-Expert software, version 14) with three parameters was used to optimize the nanoparticles after creating them using the ion gelation method. The chitosan and Tween 20 contents and the stirring speed were chosen as the independent variables, and their separate and combined effects on particle size (Y1), polydispersity index (Y2) and entrapment efficiency (Y3) were observed. The optimized formulation showed a particle size of 51 nm, an entrapment efficiency of 84.54% and a polydispersity index of 0.391. Physicochemical characterization, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), a drug release study, an ex vivo permeation study, and an antioxidant study were performed. Confocal laser scanning microscopy (CLSM) images demonstrated that chitosan nanoparticles loaded with rhodamine B-laden SCHA extract had superior penetration compared to the control (rhodamine B solution). Furthermore, compared to conventional ascorbic acid (IC50 = 45 µg/mL), a superior antioxidant activity was discovered for SCHA-CS-NPs (IC50 = 86.45 ± 2.24 µg/mL), while SCHA-CS-NPs also exhibited strong antidiabetic potential (IC50 = 93.71 ± 1.79 µg/mL) compared to standard acarbose (IC50 = 97.25 ± 1.43 µg/mL). The overall results demonstrated that SCHA-CS-NPs are a promising and efficient formulation for oral delivery.

Formulation and Characterization of Hesperidin-Loaded Transethosomal Gel for Dermal Delivery to Enhance Antibacterial Activity: Comprehension of In Vitro, Ex Vivo, and Dermatokinetic Analysis.

In this study, hesperidin was loaded into a transethosome and was developed employing the rotary evaporator method. The formulation was optimized using the Box-Behnken design (BBD). The optimized HSD-TE formulation has a spherical shape, vesicle size, polydispersity index, entrapment efficiency, and zeta potential within the range of 178.98 nm; the PDI was 0.259 with a zeta potential of -31.14 mV and % EE of 89.51%, respectively. The in vitro drug release shows that HSD-TE exhibited the release of 81.124 ± 3.45% in comparison to HSD suspension. The ex vivo skin permeation showed a 2-fold increase in HSD-TE gel permeation. The antioxidant activity of HSD-TE was found to be 79.20 ± 1.77% higher than that of the HSD solution. The formulation showed 2-fold deeper HSD-TE penetration across excised rat skin membranes in confocal laser microscopy scanning, indicating promising in vivo prospects. In a dermatokinetic study, HSD-TE gel was compared to HSD conventional gel where TE significantly boosted HSD transport in the epidermis and dermal layers. The formulation showed greater efficacy than free HSD in the inhibition of microbial growth, as evidenced by antibacterial activity on the Gram-negative and positive bacteria. These investigations found that the HSD-TE formulation could enhance the topical application in the management of cutaneous bacterial infections.

Formulation of Transliposomal Nanocarrier Gel Containing Strychnine for the Effective Management of Skin Cancer.

Strychnine (STCN) has demonstrated an exceptional anticancer effect against various cancers. However, the STCN clinical utility has been hampered by its low water solubility, restricted therapeutic window, short half-life, and significant toxicity. The objective of this investigation was to design and optimize a formulation of strychnine-loaded transliposomes (STCN-TLs) for dermal administration of STCN to treat skin cancer. The formulations of STCN-TL were examined in terms of vesicle size (VS), polydispersity index (PDI), entrapment efficiency (EE), and in vitro delivery. The improved STCN-TL formulation exhibited VS, PDI, EE, and in vitro delivery of 101.5 ± 2.14 nm, 0.218 ± 0.12, 81.74 ± 1.43%, and 85.39 ± 2.33%, respectively. In an ex vivo penetration, the created STCN-TL formulation demonstrated a 2.5-fold increase in permeability compared to the STCN solution. CLSM pictures of skin (rat) revealed that the rhodamine B-loaded transliposome preparation penetrated deeper than the rhodamine B hydroalcoholic mixture. Additionally, rat skin managed with STCN-TL nanogel exhibited a significant increase in Cskin max and AUC0-8 compared to rat skin treated with traditional STCN gel. The findings demonstrated that the transliposome preparation might be a suitable nanocarrier for the cutaneous distribution of STCN in the amelioration of skin cancer.

Resveratrol-Laden Nano-Systems in the Cancer Environment: Views and Reviews.

The genesis of cancer is a precisely organized process in which normal cells undergo genetic alterations that cause the cells to multiply abnormally, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Potential drugs that could modify these carcinogenic pathways are the ones that will be used in clinical trials as anti-cancer drugs. Resveratrol (RES) is a polyphenolic natural antitoxin that has been utilized for the treatment of several diseases, owing to its ability to scavenge free radicals, control the expression and activity of antioxidant enzymes, and have effects on inflammation, cancer, aging, diabetes, and cardioprotection. Although RES has a variety of pharmacological uses and shows promising applications in natural medicine, its unpredictable pharmacokinetics compromise its therapeutic efficacy and prevent its use in clinical settings. RES has been encapsulated into various nanocarriers, such as liposomes, polymeric nanoparticles, lipidic nanocarriers, and inorganic nanoparticles, to address these issues. These nanocarriers can modulate drug release, increase bioavailability, and reach therapeutically relevant plasma concentrations. Studies on resveratrol-rich nano-formulations in various cancer types are compiled in the current article. Studies relating to enhanced drug stability, increased therapeutic potential in terms of pharmacokinetics and pharmacodynamics, and reduced toxicity to cells and tissues are the main topics of this research. To keep the readers informed about the current state of resveratrol nano-formulations from an industrial perspective, some recent and significant patent literature has also been provided. Here, the prospects for nano-formulations are briefly discussed, along with machine learning and pharmacometrics methods for resolving resveratrol's pharmacokinetic concerns.

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

Standardization of Euphorbia tithymaloides (L.) Poit. (Root) by Conventional and DNA Barcoding Methods.

Adulteration and substitution of medicinal plants have become a matter of great concern in recent years. Euphorbia tithymaloides is one such medicinal plant that has gained importance but is often confused with other plants of the same species. In order to address this issue, this study aimed to conduct a conventional and molecular pharmacognostic study for the identification of the root of E. tithymaloides. The root of the plant was studied for the macroscopic observations, and then, the root was ground into coarse powder for microscopic studies and to determine the physiochemical properties. The powder was subjected to extraction with solvents such as ethanol, ethanol/water (1:1), hexane, and ethyl acetate. The extracts were then used for qualitative and quantitative (phenol, alkaloids, and flavonoids) phytochemical analysis. The molecular study was performed with the DNA barcoding technique. The DNA was extracted from the root of the plant, and its purity was examined by gel electrophoresis (1% w/v). The DNA was then amplified using an Applied Biosystems 2720 thermal cycler for the rbcL, matK, and ITS primers. The amplified primers were sequenced with a 3130 Genetic Analyzer, and the generated sequences were searched for similarity in the GenBank Database using the nucleotide BLAST analysis. The micro- and macroscopic studies revealed the morphological and organoleptic characters as well as the presence of medullary rays, fiber, cork, sclereids, parenchymal cells, and scalariform vessels. The physiochemical properties were found within the limit. The phytochemical analysis revealed the presence of terpenoids, flavonoids, saponins, and alkaloids. In addition, the alkaloidal content was high in the ethanol extract (63.04 ± 3.08 mg At E/g), while the phenol content was high in the hexane extract (10.26667 ± 1.77 mg At E/g), and the flavonoid content was high in the ethyl acetate extract (41.458 ± 1.33 mg At E/g). After the BLAST analysis from the GenBank database, the rbcL, ITS, and matK primers showed a similarity percentage of 99.83, 99.84, and 100. The phylogenetic tree for the species closest to each primer was generated using the MEGA 6 software. The matK loci had the highest percentage similar to the rbcL and ITS loci, indicating that the matK loci can be used to identify the root of E. tithymaloides as a standalone. The results from this study can be used to establish a quality standard for E. tithymaloides that will ensure its quality and purity.

Trofinetide for Rett Syndrome: Highlights on the Development and Related Inventions of the First USFDA-Approved Treatment for Rare Pediatric Unmet Medical Need.

Rett syndrome (RTT) is a rare disability causing female-oriented pediatric neurodevelopmental unmet medical need. RTT was recognized in 1966. However, over the past 56 years, the United States Food and Drug Administration (USFDA) has authorized no effective treatment for RTT. Recently, Trofinetide was approved by the USFDA on 10 March 2023 as the first RTT treatment. This article underlines the pharmaceutical advancement, patent literature, and prospects of Trofinetide. The data for this study were gathered from the PubMed database, authentic websites (Acadia Pharmaceuticals, Neuren Pharmaceuticals, and USFDA), and free patent databases. Trofinetide was first disclosed by Neuren Pharmaceuticals in 2000 as a methyl group containing analog of the naturally occurring neuroprotective tripeptide called glycine-proline-glutamate (GPE). The joint efforts of Acadia Pharmaceuticals and Neuren Pharmaceuticals have developed Trofinetide. The mechanism of action of Trofinetide is not yet well established. However, it is supposed to improve neuronal morphology and synaptic functioning. The patent literature revealed a handful of inventions related to Trofinetide, providing excellent and unexplored broad research possibilities with Trofinetide. The development of innovative Trofinetide-based molecules, combinations of Trofinetide, patient-compliant drug formulations, and precise MECP2-mutation-related personalized medicines are foreseeable. Trofinetide is in clinical trials for some neurodevelopmental disorders (NDDs), including treating Fragile X syndrome (FXS). It is expected that Trofinetide may be approved for treating FXS in the future. The USFDA-approval of Trofinetide is one of the important milestones for RTT therapy and is the beginning of a new era for the therapy of RTT, FXS, autism spectrum disorder (ASD), brain injury, stroke, and other NDDs.

A Low-Profile Dielectric Resonator Antenna Array for OAM Waves Generation at 5G NR Bands.

This paper presents the generation of orbital angular momentum (OAM) vortex waves with mode +1 using dielectric resonator antenna (DRA) array. The proposed antenna was designed and fabricated using FR-4 substrate to generate OAM mode +1 at 3.56 GHz (5G new radio band). The proposed antenna consists of 2 × 2 rectangular DRA array, a feeding network, and four cross slots etched on the ground plane. The proposed antenna succeeded in generating OAM waves; this was confirmed by the measured radiation pattern (2D polar form), simulated phase distribution, and intensity distribution. Moreover, mode purity analysis was carried out to verify the generation of OAM mode +1, and the purity obtained was 53.87%. The antenna operates from 3.2 to 3.66 GHz with a maximum gain of 7.3 dBi. Compared with previous designs, this proposed antenna is low-profile and easy to fabricate. In addition, the proposed antenna has a compact structure, wide bandwidth, high gain, and low losses, thus meeting the requirements of 5G NR applications.