The contemplation of amylose for the delivery of ulcerogenic nonsteroidal anti-inflammatory drugs.

This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked with nonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility and biodegradability, as well as its capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.

The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis.

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.

Cationic cycloamylose based nucleic acid nanocarriers.

Nucleic acid delivery by viral and non-viral methods has been a cornerstone for the contemporary gene therapy aimed at correcting the defective genes, replacing of the missing genes, or downregulating the expression of anomalous genes is highly desirable for the management of various diseases. Ostensibly, it becomes paramount for the delivery vectors to intersect the biological barriers for accessing their destined site within the cellular environment. However, the lipophilic nature of biological membranes and their potential to limit the entry of large sized, charged, hydrophilic molecules thus presenting a sizeable challenge for the cellular integration of negatively charged nucleic acids. Furthermore, the susceptibility of nucleic acids towards the degrading enzymes (nucleases) in the lysosomes present in cytoplasm is another matter of concern for their cellular and nuclear delivery. Hence, there is a pressing need for the identification and development of cationic delivery systems which encapsulate the cargo nucleic acids where the charge facilitates their cellular entry by evading the membrane barriers, and the encapsulation shields them from the enzymatic attack in cytoplasm. Cycloamylose bearing a closed loop conformation presents a robust candidature in this regard owing to its remarkable encapsulating tendency towards nucleic acids including siRNA, CpG DNA, and siRNA. The presence of numerous hydroxyl groups on the cycloamylose periphery provides sites for its chemical modification for the introduction of cationic groups, including spermine, (3-Chloro-2 hydroxypropyl) trimethylammonium chloride (Q188), and diethyl aminoethane (DEAE). The resulting cationic cycloamylose possesses a remarkable transfection efficiency and provides stability to cargo oligonucleotides against endonucleases, in addition to modulating the undesirable side effects such as unwanted immune stimulation. Cycloamylose is known to interact with the cell membranes where they release certain membrane components such as phospholipids and cholesterol thereby resulting in membrane destabilization and permeabilization. Furthermore, cycloamylose derivatives also serve as formulation excipients for improving the efficiency of other gene delivery systems. This review delves into the various vector and non-vector-based gene delivery systems, their advantages, and limitations, eventually leading to the identification of cycloamylose as an ideal candidate for nucleic acid delivery. The synthesis of cationic cycloamylose is briefly discussed in each section followed by its application for specific delivery/transfection of a particular nucleic acid.

Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

Synthesis and evaluation of amylose-mefenamic acid conjugates as colon-targeting prodrugs.

Aim: Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Materials & methods: Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Results: Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Conclusion: Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.

Anticancer and chemopreventive potential of Morinda citrifolia L. bioactive compounds: A comprehensive update.

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.

Unraveling the impact of miR-21 on apoptosis regulation in glioblastoma.

Glioblastoma is a prevalent form of carcinoma that exhibits a greater incidence rate across diverse demographics globally. Despite extensive global efforts, GBM continues to be a highly lethal disease that is characterized by a grim prognosis. There is a wealth of evidence suggesting that the pathophysiology of GBM is associated with the dysregulation of numerous cellular and molecular processes. The etiology of GBM may involve various cellular and molecular pathways, including EGFR, PDCD4, NF-κB, MAPK, matrix metalloproteinases, STAT, and Akt. MicroRNAs, short non-coding RNA molecules, regulate gene expression and mRNA translation after transcription but before translation to exert control over a wide range of biological functions. Extensive research has consistently demonstrated the upregulation of miRNA-21 in glioma, indicating its involvement in diverse biological pathways that facilitate tumor cell survival. By explaining the intricate interplay between miR-21 and the regulation of apoptosis in GBM, this review has the potential to significantly enhance our comprehension of the illness and provide potential targets for therapeutic intervention.

From carcinogenesis to therapeutic avenues: lncRNAs and mTOR crosstalk in lung cancer.

Long non-coding RNAs (lncRNAs) have been demonstrated to have a crucial function in the modulation of the activity of genes, impacting a variety of homeostatic processes involving growth, survival, movement, and genomic consistency. Certain lncRNAs' aberrant expression has been linked to carcinogenesis, tumor growth, and therapeutic resistance. They are beneficial for the management of malignancies since they can function as cancer-causing or cancer-suppressing genes and behave as screening or prognosis indicators. The modulation of the tumor microenvironment, metabolic modification, and spread have all been linked to lncRNAs in lung cancer. Recent research has indicated that lncRNAs may interact with various mTOR signalling systems to control expression in lung cancer. Furthermore, the route can affect how lncRNAs are expressed. Emphasizing the function of lncRNAs as crucial participants in the mTOR pathway, the current review intends to examine the interactions between the mTOR cascade and the advancement of lung cancer. The article will shed light on the roles and processes of a few lncRNAs associated with the development of lung cancer, as well as their therapeutic prospects.

Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship.

Lignans are plant-derived polyphenolic compounds with a plethora of biological applications. Also, regarded as phytoestrogens, the lignans offer a variety of health benefits of which the anti-cancer effects are the most attractive. Honokiol is a lignan isolated from various parts of trees belonging to the genus Magnolia. The bioactivity of honokiol is attributed to its characteristic physical properties, which include small size and the presence of two phenolic groups that may interact with proteins in cell membranes via hydrophobic interactions, aromatic pi orbital co-valency, and hydrogen bonding. The hydrophobicity of honokiol enables its rapid dissolution in lipids and the crossing of physiological barriers, including the blood-brain barrier and cerebrospinal fluid. These factors contribute towards the high bioavailability of honokiol which further support its candidature in medicinal research. Therefore, the anticancer properties of honokiol are of particular interest as many of the contemporary anticancer drugs suffer from bioavailability drawbacks, which necessitates the identification and development of novel candidate molecules directed as anticancer chemotherapeutics. The antioncogenic profile of honokiol also arises from the regulation of various signalling pathways associated with oncogenesis, arresting of the cell cycle by regulation of cyclic proteins, upregulation of epithelial markers and downregulation of mesenchymal markers leading to the inhibition of epithelial-mesenchymal transition, and preventing the metastasis by restricting cell migration and invasion due to the downregulation of matrix-metalloproteinases. In this review, we discuss the anticancer properties of honokiol.

Layered double hydroxide nanocarriers: potential delivery systems for mefenamic acid.

Tweetable abstract Layered double hydroxide nanocarriers are capable of intercalating hydrophobic NSAIDs, such as mefenamic acid, which improves their pharmacokinetics and bioavailability.

Hybridization of antimicrobial oxazolidinones with commercial drugs: A fight against the "superbugs".

Antimicrobial resistance caused by the emergence of antibiotic-resistant microbes, termed as "superbugs," poses a grave healthcare concern in the contemporary era. Though this phenomenon is natural, an incessant use of antibiotics due to their unregulated over-the-counter availability, and a lack of compliance with the legislation seem to be major contributing factors. This phenomenon has further complicated the treatment of common infectious diseases thereby leading to prolonged illness, disability, and even death. In addition, a sizeable impact on the healthcare cost is met due to a prolonged stay at the medical facilities to receive an intensive care. Overall, the gains of "Millennium Development Goals" and the accomplishment of Sustainable Development Goals are at risk due to the emerging antimicrobial resistance. Since an early identification and development of novel antibiotic classes that evade antimicrobial resistance appears improbable, the strategy of hybridization of the existing antibiotics with efficacious pharmacophores and drug molecules with a different mechanism of antimicrobial action can be a silver lining for the management of superbugs. In this regard, we aim to provide a perspective for the applicability of the hybridization of oxazolidinone class of antibiotics with other drugs for evading antimicrobial resistance.

Synthesis and biological profile of benzoxazolone derivatives.

The benzoxazolone nucleus is an ideal scaffold for drug design, owing to its discrete physicochemical profile, bioisosteric preference over pharmacokinetically weaker moieties, weakly acidic behavior, presence of both lipophilic and hydrophilic fragments on a single framework, and a wider choice of chemical modification on the benzene and oxazolone rings. These properties apparently influence the interactions of benzoxazolone-based derivatives with their respective biological targets. Hence, the benzoxazolone ring is implicated in the synthesis and development of pharmaceuticals with a diverse biological profile ranging from anticancer, analgesics, insecticides, anti-inflammatory, and neuroprotective agents. This has further led to the commercialization of several benzoxazolone-based molecules and a few others under clinical trials. Nevertheless, the SAR exploration of benzoxazolone derivatives for the identification of potential "hits" followed by the screening of "leads" provides a plethora of opportunities for further exploration of the pharmacological profile of the benzoxazolone nucleus. In this review, we aim to present the biological profile of different derivatives based on the benzoxazolone framework.

Targeted delivery of fenamates with aminated starch.

Aim: To develop controlled-release tablets based on aminated starch. Materials & methods: Aminated starch was characterized with Fourier transform infrared and x-ray diffraction. Thermogravimetric analysis confirmed the preferential oxidation of crystalline region of starch. Results: The tablets achieved an initial fast release of fenamates, which slows down after 12 h. Drug release was not completed in the simulated intestinal media, which may be due to the stability of imine bond in aminated starch at weakly acidic pH. Drug release was completed in simulated acidic media due to the hydrolysis of imine functionality at strongly acidic pH. Conclusion: Aminated starch with an imine functionality may serve as intestine targeted, controlled drug-delivery system. Mucoadhesive potential of tablets further supports this observation.

The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review.

Cytotoxic drugs have long been recognised to kill cancer cells through apoptosis. According to a current study, pyroptosis inhibits cell proliferation and shrinks tumors. Pyroptosis and apoptosis are caspase-dependent programmed cell death (PCD) processes. Inflammasomes activate caspase-1 and latent cytokines, including IL-1ß and IL-18, to cleave gasdermin E (GSDME) and induce pyroptosis. Gasdermin proteins activate caspase-3 to induce pyroptosis, which is associated with tumour genesis, development, and therapy response. These proteins may serve as therapeutic biomarkers for cancer detection, and their antagonists may be a new target. Caspase-3, a crucial protein in both pyroptosis and apoptosis, governs tumour cytotoxicity when activated, and GSDME expression modulates this. Once active caspase-3 cleaves GSDME, its N-terminal domain punches holes in the cell membrane, causing it to expand, burst, and die. To understand the cellular and molecular mechanisms of PCD mediated by caspase-3 and GSDME, we focused on pyroptosis. Hence, caspase-3 and GSDME may be promising targets for cancer treatment.

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms.

Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology.