Empowered by nanotechnology, messenger RNA (mRNA) therapeutics have shown a rapid evolution post COVID-19 from a conceptual platform to a clinically validated modality, and they diversified into oncology, cardiovascular diseases, and rare disorders. As a template for in situ protein production, it offers several advantages over traditional proteins and DNA drugs. The intrinsic stability of mRNA and its sensitivity to innate immune sensing hinder its capacity for immediate cellular entry, necessitating its need for a delivery system to obtain optimal therapeutic potential. This review explores the innovations in nanocarrier engineering, design principles for lipid nanoparticles-mRNA (LNPs) platforms, and their clinical translation across the prominent indications. It also addresses their safety, immunogenicity, and scalability while addressing the key limitations and manufacturing scalability through comparative platform analysis. Although LNPs usually dominate their delivery through encapsulation and manufacturability, their limitations, like repeat dose reactogenicity and liver tropism, require next-generation designs like SORT lipids, stimuli-responsive hybrids for extrahepatic targeting. In oncology, LNP-mRNA drives the neoantigen vaccines, and rare diseases leverage the transient enzyme replacement. While the safety profiles highlight the innate immune tuning through nucleoside mods and lipid biodegradability, chronic administration risks are still persistent. While there are novel scalability options like microfluidic mixing to support the production gaps in organ selectivity and durability, their adoption is hindered. We outline the future directions to perceive mRNA’s full potential as a broader therapeutic class.

This study explores the anticancer and antioxidant potential of Heliotropium indicum L. through integrated phytochemical, biological, and computational approaches. GC-MS analysis identified phenol, 3,5-bis(1,1-dimethylethyl) as a major constituent. The chloroform fraction (CHF) exhibited significant in vivo antitumor activity in an Ehrlich ascites carcinoma (EAC) model, showing 76.39% tumor growth inhibition, comparable to bleomycin (80.36%). CHF also demonstrated potent cytotoxicity (LC50 = 28.96 μg/mL) in a brine shrimp assay and protected against AAPH-induced oxidative DNA damage. Molecular docking revealed strong binding of key compounds to topoisomerase II, supported by stable molecular dynamics simulations and favorable MM-PBSA binding energies. These findings highlight H. indicum as a promising source of anticancer and antioxidant agents, warranting further mechanistic and preclinical investigation.

Background: Immunomodulatory compounds can modify or regulate the immune responses. Given that vaccine-induced immune responses can vary in magnitude and durability depending on antigen properties and adjuvant selection. Immunomodulators that enhance antigen-specific immune responses with low toxicity may complement existing adjuvant systems. Recent studies indicate that adenosine receptor–mediated signaling can modulate dendritic cell (DC) function through mechanisms distinct from classical pathogen-associated molecular pattern (PAMP)-driven Toll-like receptor pathways. Methods: In this context, the present study comparatively evaluates poly-(lactic-co-glycolic acid) (PLGA) microparticle–encapsulated β-L-adenosine (BLA MPs) alongside established FDA-approved adjuvants to assess their immunomodulatory potential under limited-antigen conditions. FDA-approved PLGA was used to encapsulate BLA in combination with multiple viral antigens, including H1N1 influenza, Zika virus, and canine coronavirus, to enable sustained delivery, antigen protection, and efficient uptake by antigen-presenting cells. Results: Physicochemical characterization demonstrated uniform particle size distribution, a low polydispersity index, and a stable negative surface charge. Release studies showed more than 50% payload release within 12 h, with release kinetics best described by the Korsmeyer–Peppas model. Cytotoxicity evaluation using DC2.4 cells confirmed that BLA MPs were non-cytotoxic at concentrations up to 250 μg/mL. Comparative in vitro immunological assessments revealed that BLA MPs induced dendritic cell activation, including upregulation of antigen-presenting and co-stimulatory molecules, at levels largely comparable to those observed with Alum- and MF59-based formulations across multiple antigen groups. Nitric oxide production remained within comparable ranges, indicating balanced immunostimulatory activity without excessive inflammatory signaling. In select conditions, co-formulation of BLA MPs with MF59 further enhanced DC activation, supporting its role as a complementary immunomodulatory component. Conclusion: These findings align with previously reported adenosine-dependent pathways involved in DC maturation and antigen presentation. Overall, this comparative study demonstrates that PLGA-encapsulated β-L-adenosine functions as an effective immunomodulatory agent, with performance comparable to that of established FDA-approved adjuvants across diverse vaccine antigens. Further in vivo studies are warranted to evaluate dose dependency, cytokine profiles, and antibody responses to define its role within combinatorial vaccine adjuvant strategies.

The goal of this effort was to create mesoporous nanoparticles (MSNs) decorated with amine groups and loaded with liraglutide (LRT) for oral delivery. Amine-decorated MSNs were helpful for peptide entrapment and prolonged release of liraglutide, a GLP-1 analog. Liraglutide-loaded MSNs were made by using acetonitrile and water sol-gel techniques. Over the course of 24 h, the particles provided consistent drug release, with cumulative release reaching up to 90% in vitro. Differential dynamic light scattering, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis and differential scanning calorimetry (DSC) were used to characterize the synthesized formulation. The MTT assay was used to evaluate cell viability along with the hemolysis assay and was found to be safe. Particle size determination was performed by a zeta sizer; the size was 286 nm [Formula: see text], and the PDI and zeta potential were 0.29 and +8.89 mV, respectively. The drug entrapment efficiency was also very good at 56% ± 9%, and the drug release was more than 90.0% ± 9 within 24 h at all pH values tested. The efficacy of the particles was examined in a rat model of diabetes and contrasted with that of a group that received daily injections of liraglutide. Between 0 and 5 days after the start of treatment, lower blood sugar levels were observed in the particle treatment groups than in the injection groups. Overall, the liraglutide-loaded MSNs created in this work are effective in a rat model of diabetes, and as a result, we believe that they have great potential for clinical application.

Ionic liquids (ILs) are salts with poorly coordinated ions, allowing them to exist in a liquid phase below 100 °C or at room temperature. Therefore, they are best described as room temperature ionic liquids (RTILs). In ionic liquids, the presence of a delocalized charge in at least one ion, coupled with an organic component, inhibits the establishment of a stable solid crystal lattice. Due to their flexible properties and several distinctive characteristics, such as high ionic conductivity, high solvation power, thermal stability, low volatility, and recyclability, ILs have been extensively used in chemical industries. In addition to their various other applications, they also hold potential for drug formulation development. Ionic liquids can be used as solubility enhancers, permeability enhancers, stabilizers, targeted delivery inducers, stealth property providers, or bioavailability enhancers. Moreover, ILs hold significant potential in vaccine formulation. Many new vaccines are in the pipeline with different types of antigens; however, the existence of only a limited number of adjuvants hinder their potential use. Thus, developing new, highly effective, low-cost adjuvant preparations is a central interest among formulation scientists. With their unique properties and biological functions, ILs can be highly promising candidates for new types of vaccines.

The aim of this study was to develop a ciclopirox (CXP) topical nano spray using nanotechnology to enhance drug bioavailability and skin absorption. A precipitation method was employed to incorporate CXP in its nano particulate form, using chitosan as the polymer. Chitosan nanoparticles (CT NPs) possess unique properties that make them highly suitable for biological applications. The study focused on investigating the penetration behavior of chitosan nanoparticles (nano spray) through artificial skin, with the goal of developing them as effective skin delivery systems for medications. The nanoparticles had an average size of 640 nm, with a positive or negative surface potential and a polydispersity index (PDI) of 0.298. A thorough analysis of the nano spray was conducted using several scientific techniques, including X-ray diffractometry, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), as well as in vitro release and diffusion studies. Additionally, cell viability was evaluated using the MTT assay, and blood compatibility was tested through a hemolysis test. The study also assessed the levels of the anti-inflammatory cytokine IL-2 in the lungs of mice using RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR). The drug dissolution and diffusion rates showed a significant improvement compared to the pure reference sample. Therefore, the CXP nano spray appears to be an efficient and practical method to enhance skin penetration, bioavailability, and permeability. Based on the results, the CXP nano spray holds potential as a promising treatment for fungal infections, particularly for skin diseases.

Polyurethane/hydroxyapatite (PU/HA) composites are well-known for various biomedical applications. This study reports a chemical approach to improve the interaction between HA and PU matrix. HA was surface-modified with 1,6-hexamethylene diisocyanate (HMDI). First, an isocyanate-modified HA (IHA) was synthesized by hydro-thermal method. Second, IHA was incorporated into a separately synthesized thermoplastic PU by a solvent casting technique. A series of PU/IHA composites was prepared by varying PU᾿s soft and hard segments. The IHA was added to PU (5 and 10 %). The FTIR spectra exhibited characteristic bands of urethane and HA, confirming the synthesis of the composites. XRD study showed the crystallite size of IHA (20 Å) with hexagonal geometry and an amorphous to semicrystalline nature of composites. SEM showed that composites displayed porous and granular morphology. The TGA thermograms of the composites revealed the thermal stability up to 400 °C. The IHA addition considerably improved hydrophilicity and degradation of the composites in simulated body fluid (SBF). MTT assay revealed improved cytocompatibility (> 80 %) of the composites. These results demonstrated an appreciable improvement in structure, morphology, hydrophilicity, degradation, and cytocompatibility of PU/IHA composites by chemical modification of HA. Hence, these composites possess remarkable potential for biomedical applications such as tissue regeneration.

Gliclazide (GLC)-loaded Aerosil 380 solid dispersion (GA-SD)-based tablets with co-processed excipient composites were formulated to critically evaluate the physicochemical performance of the resulting tablets with enhanced drug release. GA-SD was prepared using the solvent evaporation method with a 1:1 weight ratio based on a previously published report, and its drug release patterns were evaluated. Processed excipient composites, such as lactose-starch-povidone (LSP) and lactose-starch-povidone-sodium starch glycolate (LSPS), were prepared via a coprocessing strategy and evaluated for their ability to perform specific functions. At predetermined combination levels, aqueous dispersions of primary excipients were physically agglomerated at a controlled temperature below the gelatinization temperature (55 °C) before drying at 60 °C for 48 h. GA-SD and co-processed excipients (LSP and LSPS) were utilized to produce tablet batches GAC1 to GAC8 (Gliclazide-Aerosil 380–co-processed excipients, GAC) by direct compression. Through rigorous testing of tablet batches, the physicochemical properties of the resulting formulations were analyzed and compared to those of leading marketed formulations (MFs). FTIR studies were also conducted to detect drug-excipient interactions in the tablet formulations. The release mechanism of the GLC was determined by studying the dissolution process with various kinetic models. The GAC tablets were subjected to 40 °C/75

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is involved in bacterial communication. DPD is the precursor of signal molecule autoinducer-2 (AI-2) and has high potential to be used as a vaccine adjuvant. Vaccine adjuvants are compounds that enhance the stability and immunogenicity of vaccine antigens, modulate efficacy, and increase the immune response to a particular antigen. Previously, the microparticulate form of (S)-DPD was found to have an adjuvant effect with the gonorrhea vaccine. In this study, we evaluated the immunogenicity and adjuvanticity of several synthetic analogs of the (S)-DPD molecule, including ent—DPD((R)-4,5-dihydroxy-2,3-pentanedione), n-butyl—DPD ((S)-1,2-dihydroxy-3,4-octanedione), isobutyl—DPD ((S)-1,2-dihydroxy-6-methyl-3,4-heptanedione), n-hexyl—DPD ((S)-1,2-dihydroxy-3,4-decanedione), and phenyl—DPD ((S)-3,4-dihydroxy-1-phenyl-1,2-butanedione), in microparticulate formulations. The microparticulate formulations of all analogs of (S)-DPD were found to be noncytotoxic toward dendritic cells. Among these analogs, ent—DPD, n-butyl—DPD, and isobutyl—DPD were found to be immunogenic toward antigens and showed adjuvant efficacy with microparticulate gonorrhea vaccines. It was observed that n-hexyl—DPD and phenyl—DPD did not show any adjuvant effect. This study shows that synthetic analogs of (S)-DPD molecules are capable of eliciting adjuvant effects with vaccines. A future in vivo evaluation will further confirm that these analogs are promising vaccine adjuvants.

The efficiency of vaccines has been significantly enhanced since the discovery of adjuvants to induce innate and adaptive immunity. Adjuvants add significant value to vaccine formulations by enhancing antigen-specific immunological responses. Adjuvants can increase humoral and cell-mediated immunity, allowing for prolonged protection against the pathogen. The amount of antigen and dose required is reduced by adding an adjuvant. The selection and screening process of adjuvants is vital for designing and formulating human vaccines. Several platforms of carriers exist that can aid in the process of developing an adjuvant. Carrier systems are essential components of vaccine formulation to induce intended immunogenic activity. Carrier systems are beneficial in inducing immunogenic responses when vaccines are formulated in the particulate form that includes whole cells and mainly in emerging subunit protein/peptide-based vaccines. Several carrier systems have been explored and utilized in vaccine and cancer antigen formulations to achieve T-cell-mediated long-term immunologic responses.

This study investigates the structural, morphological, optical, and electrical characteristics of Al3+ and Sn4+ doped ZnO nano-crystalline thin films fabricated using a sol–gel spin coating technique. The thin-films, with a uniform thickness of 200 nm (2

Objective: Preeclampsia (PreE) is a hypertensive pregnancy disorder, which occurs in approximately 10% of all gestations. The literature suggests potential therapeutic role of H2 relaxin in PreE. A novel H2 relaxin B-chain-only peptide variant B7-33 has recently been developed. This single-chain peptide displayed equivalent efficacy to the natural H2 relaxin in several functional assays both in vitro and in vivo. The Aim of this study is to evaluate whether B7-33 attenuates preE syndrome in rodent models of PreE. Design and method: Rat Model 1. The efficacy of B7-33 was evaluated in the Reduction of Uterine Perfusion Pressure (RUPP) model as described previously. RUPP rats are randomly assigned to 4 groups (N=8/group): 1) vehicle, 2) B733; 3) B733-Fc; and 4) B733-HSA. Rats are dosed twice weekly (i.v.) from GD10 to GD 20. Rat Model 2. Timed-pregnant rats are used, and the model is conducted as previously described. DOCA and saline administration begin at approximately GD2. Three groups of animals are studied (n=8 per group). 1) normal pregnant rats; 2) pregnant animals injected (i.p.) initially with 12.5 mg of DOCA, followed by a weekly injection of 6.5 mg, and whose drinking water was replaced with 0.9% saline; 3) rats administered DOCA and saline as for Group 2, and given B733 35 ug i.p. biweekly from GD10-20. BP, proteinuria and inflammatory markers were evaluated. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test. Results: RUPP rats have increased MAP, plasma TNF-alpha, and plasma sFlt-1 along with decreased NO index compared to normal pregnancy. Treatment with B733 and B7-33 fusion proteins lowers MAP, TNF-alpha, and sFlt-1 back to that of normal pregnancy. B7-33 data are consistent with earlier data with serelaxin in the RUPP model. All fusions tested ameliorate hypertension in the RUPP animals. B7-33 normalizes BP and proteinuria in the DOCA rat model of preE. Conclusions: Both B7-33 and B7-33 fusion proteins attenuate preE syndrome in RUPP and DOCA rat models of PreE. We conclude that B7-33 is an ideal candidate for development as a novel therapeutic in preE.

Herbal spices are an agricultural commodity, economically very important and beneficial in primary healthcare in the food and medicine sectors. Herbal spices are used as food flavoring agents as well as in phytotherapies throughout the world and have nutritive benefits. The food and medicine industries widely employ artificial or natural adulteration to retard the deterioration and utilization of these adulterants in food and medicine products has given rise to significant apprehension among consumers, primarily stemming from the potential health risks that they pose. Thus, their characterization for the purpose of identification, origin, and quality assurance is mandatory for safe human consumption. Here, we studied 22 samples of commonly traded herbal spices that belong to 20 different genera and 21 species comprising 14 families, investigated macroscopically or organoleptically as well as histologically under microscopic examination. In this study, we provide details on organoleptic features including appearance, taste, odor, color, shape, size, fractures, types of trichomes, and the presence of lenticels among the examined herbal spices and these features have great significance in the detection of both natural as well as artificial deterioration. In terms of microscopic characterization, each examined plant part comprising different anatomical characteristics has taxonomic importance and also provides useful information for authentication from natural adulterants. Furthermore, the studied taxa were also described with nutritive and therapeutic properties. For condiments, herbal beverages and medicinal purposes, different herbal parts such as leaves, floral buds, seeds, fruit, and accessory parts like mericarp, rhizome, bulbs, and bark were used and commercially traded. Similarly, in this study, the leaves of Cinnamomum tamala and Mentha spicata, the floral buds of Syzygium aromaticum, the seeds of Amomum subulatum, Brassica nigra, Punica granatum, Myristica fragrans, Phyllanthus emblica, and Elettaria cardamomum, the mericarp of Coriandrum sativum, and Cuminum cyminum were observed. As a result, we show the potential of herbal spices as a source of many valuable phytochemicals and essential nutrients for food, nutraceutical, and homoeopathic medicine.

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates’ ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay’s effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay’s potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations.

This study aims to investigate a potential alternative for MSP1D1 protein to develop a lipid polymer hybrid nanoparticle (LPHN) system of curcumin using poloxamer 407 and its targeted drug delivery to the brain. Design of experiment (DoE) was used to optimize the lipid nanodisc and LPHN delivery system of curcumin by the thin film hydration method. Solid-state characterization of the optimized lipid nanodiscs and LPHNs was performed using DLS, TEM, SEM, PXRD, and DSC. In vitro release, stability study, and in vivo anti-inflammatory and bioavailability studies in mice brains were performed for the optimized LPHN delivery system. DLS and microscopic data showed that the average sizes of the lipid nanodisc and LPHN systems were 125–198 nm and 135–240 nm, respectively. The LPHN delivery system of curcumin exhibited high entrapment efficiency (95.7 ± 2.2

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain–Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of −19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.

Background: Preeclampsia (PE) is a hypertensive pregnancy disorder, which occurs in approximately 10% of all gestations. The literature suggests the potential therapeutic role of H2 relaxin in PE. A novel H2 relaxin B-chain-only peptide variant B7-33 (27 amino acids without any disulfide bonds) has recently been developed. Objective: The goal of this study was to test the hypothesis that a novel H2 relaxin B-chain-only peptide variant B7-33 could improve the pathophysiology of placental ischemia in the Reduced Uterine Perfusion Pressure (RUPP) rat model of PE. Methods: The efficacy of B7-33 was evaluated in the RUPP model as described previously. RUPP rats are randomly assigned to 4 groups (N=8/group): 1) vehicle, 2) B733; 3) B733-Fc; and 4) B733-HSA. Rats are dosed twice weekly (i.v.) from GD10 to GD 20. On GD 18, rats are anesthetized with isoflurane, and carotid arterial catheters are inserted into the carotid artery, tunneled under the skin, and externalized at the back of the neck. On the following day, mean arterial pressure (MAP) is monitored with a pressure transducer (Cobe III Tranducer CDX Sema) and recorded continuously for 30 min. On GD18, uterine artery resistance index (UARI) of rats is measured by Doppler sonography. The nitric oxide bioavailability, soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) were measured by commercially available kits. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test. Results: The RUPP rats have increased MAP (122.2 ± 8.1 mm Hg), plasma TNF-α (223 ±11.4 pg/mL), and plasma sFlt-1(863 ±18.2 pg/mL) along with decreased NO index (14±2 µM) compared to normal pregnancy: MAP (102 ± 5.2 mm Hg); plasma TNF-α (28 ± 4.1 pg/mL); plasma sFlt-1(244 ± 9.4 pg/mL) and NO index (26 ±4.1 µM). Treatment with B733 and B7-33 fusion proteins significantly (*p<0.05) lowers MAP, plasma TNF-α, and plasma sFlt-1 and increased NO index back to that of normal pregnancy. The B7-33 data are consistent with earlier data with serelaxin in the RUPP model. All fusions tested ameliorate hypertension in the RUPP animals. B7-33 normalizes BP and proteinuria in the DOCA rat model of preE. Conclusion: The conclusion of the study is that both B7-33 and B7-33 fusion proteins demonstrate efficacy in attenuating the symptoms of PE including hypertension and inflammation in RUPP model. We conclude that B7-33 is an ideal candidate for development as a novel therapeutic in preE.

Background:Intrauterine growth restriction (IUGR) and preeclampsia (PE) are intricately linked with specific maternal health conditions, exhibit shared placental abnormalities, and play pivotal roles in precipitating preterm birth (PTB) incidences. However, the molecular mechanism underlying the association between PE and IUGR has not been determined. Therefore, we aimed to analyze the data of females with PE and those with PE + IUGR to identify the key gene(s), their molecular pathways, and potential therapeutic interactions.Methods:In this study, a comprehensive relationship analysis of both PE and PE + IUGR was conducted using RNA sequence datasets. Using two datasets (GSE148241 and GSE114691), differential gene expression analysis via DESeq2 through R-programming was performed. Gene set enrichment analysis was performed using ClusterProfiler, protein‒protein interaction (PPI) networks were constructed, and cluster analyses were conducted using String and MCODE in Cytoscape. Functional enrichment analyses of the resulting subnetworks were performed using ClueGO software. The hub genes were identified under both conditions using the CytoHubba method. Finally, the most common hub protein was docked against a library of bioactive flavonoids and PTB drugs using the PyRx AutoDock tool, followed by molecular dynamic (MD) simulation analysis. Pharmacokinetic analysis was performed to determine the ADMET properties of the compounds using pkCSM.Results:We identified eight hub genes highly expressed in the case of PE, namely, PTGS2, ENG, KIT, MME, CGA, GAPDH, GPX3, and P4HA1, and the network of the PE + IUGR gene set demonstrated that nine hub genes were overexpressed, namely, PTGS2, FGF7, FGF10, IL10, SPP1, MPO, THBS1, CYBB, and PF4. PTGS2 was the most common hub gene found under both conditions (PE and PEIUGR). Moreover, the greater (−9.1 kcal/mol) molecular binding of flavoxate to PTGS2 was found to have satisfactory pharmacokinetic properties compared with those of other compounds. The flavoxate-bound PTGS2 protein complex remained stable throughout the simulation; with a ligand fit to protein, i.e., a RMSD ranging from ∼2.0 to 4.0 Å and a RMSF ranging from ∼0.5 to 2.9 Å, was observed throughout the 100 ns analysis.Conclusion:The findings of this study may be useful for treating PE and IUGR in the management of PTB.

Vaccines have been one of the most important medical inventions of modern times. Vaccination against infectious diseases has protected humans against the onslaught of deadly microorganisms and helped sustain humanity. Early antigens consisted of live or inactivated pathogens. However, to keep up with advanced pathogens, several novel vaccines, such as subunit and nucleic acid-based vaccines, have been developed. This chapter discusses the need for novel antigens and the resulting advances made with novel vaccine antigens. The discovery of novel vaccine antigens resulted in the advent of novel delivery systems to carry the novel antigens. This chapter describes the different carrier systems, such as novel formulations used to deliver the vaccine antigens. The success of vaccines also depends on vaccine compliance by patients. Even today, several people avoid vaccination due to the fear of needles. Thus, in addition to novel antigens and carrier systems, a great deal of research has gone into novel routes of administration. In addition to being painless, novel routes of vaccine administration may also contribute to vaccine efficacy. This chapter introduces the different novel routes of vaccine administration and deliberates the different formulations used to deliver the vaccine via the novel routes. Thus, this book describes recent advances in the field of novel vaccines.