Biophysical Evaluation Research Articles

Perceived ecosystem services differ substantially from calculated services using biophysical models

ContextEcosystem services are fundamental for the well-being of residents and are an important basis for making regional sustainable development decisions. Existing studies mainly capture ecosystem services perceived by residents through questionnaires, or quantify the provision of regional ecosystem services through economic evaluation and biophysical evaluation. However, the discrepancy between model calculations and residents' perceptions remains lacking.ObjectivesRapidly urbanizing watersheds can serve as a prime example for exploring the differences in ecosystem service outcomes between the two perspectives.MethodsIn this study, we quantified the potential supply of nine ecosystem services and residents' perceptions of these services in the Guanting Reservoir basin through biophysical modelling and questionnaire surveys. We then analyzed the discrepancies between the two perspectives through the Wilcoxon signed-rank test.ResultsThe results showed that among the vast majority of the population, half of the nine ecosystem services exhibited significant differences in comparisons between perceived values and model-calculated ones. The differences were more prominent for regulating and supporting services among urban residents, while for provisioning and cultural services among rural residents.Conclusions These differences highlight the necessity to consider quantitative results from diverse perspectives as well as on the benefits of different groups of interest. In rapidly urbanizing watersheds, infrastructure should be reinforced in rural areas to enhance rural residents’ accessibility of ecosystem services. With regard to urban areas, particular attention should be directed towards changes in regulating and supporting services.

Cutibacterium acnes induces acne-like lesions in hairless mice models - A comparative study

Acne vulgaris, a chronic inflammatory skin disease with a high prevalence worldwide, necessitates reliable preclinical models for both understanding its pathogenesis and evaluating potential anti-acne therapies. This study aims to establish a robust mouse model using intracutaneous injection of Cutibacterium acnes bacterial suspension. Three hairless mouse strains (SKH-hr1, SKH-hr2 brown, and SKH-hr2 + ApoE) were systematically compared to ascertain the stains most closely resembling acne in humans. Various assessments, including photo documentation, biophysical evaluation, blood analysis, and histopathology, were conducted. Despite all strains exhibiting acne-like lesions, SKH-hr1 mice emerged as the most suitable model, demonstrating the most satisfactory results across multiple criteria. This research underscores the significance of employing hairless mice strains as models in acne studies to enhance and facilitate the development of effective therapeutic interventions.

Biocomposite Materials Derived from Andropogon halepensis: Eco-Design and Biophysical Evaluation.

This research work presents a "green" strategy of weed valorization for developing silver nanoparticles (AgNPs) with promising interesting applications. Two types of AgNPs were phyto-synthesized using an aqueous leaf extract of the weed Andropogon halepensis L. Phyto-manufacturing of AgNPs was achieved by two bio-reactions, in which the volume ratio of (phyto-extract)/(silver salt solution) was varied. The size and physical stability of Andropogon-AgNPs were evaluated by means of DLS and zeta potential measurements, respectively. The phyto-developed nanoparticles presented good free radicals-scavenging properties (investigated via a chemiluminescence technique) and also urease inhibitory activity (evaluated using the conductometric method). Andropogon-AgNPs could be promising candidates for various bio-applications, such as acting as an antioxidant coating for the development of multifunctional materials. Thus, the Andropogon-derived samples were used to treat spider silk from the spider Pholcus phalangioides, and then, the obtained "green" materials were characterized by spectral (UV-Vis absorption, FTIR ATR, and EDX) and morphological (SEM) analyses. These results could be exploited to design novel bioactive materials with applications in the biomedical field.

Albumin–Rutin Nanoparticles: Design, Characterization, and Biophysical Evaluation

The bioavailability of the administered drugs that reach the systemic circulation is the first point in resolving the pathology of patients. Albumin-based nanoparticles represent an increasingly used strategy to deliver cancer drugs into cells that otherwise cannot overcome biological barriers. In this work, rutin (Ru), a flavonoid with anticancer and antioxidant potential, was incorporated into bovine serum albumin nanoparticles (BSA-Ru NPs), developed using the desolvation method, and the entire system was characterized and evaluated by scanning electron microscopy (SEM), atomic force microscopy (AFM), and UV–Vis absorption spectroscopy. The results showed that BSA and BSA–Ru NPs are uniformly distributed, have relatively large sizes, and have a time stability of more than 60%. Furthermore, the effect of these nanohybrids on the thermal stability of liposomal membranes was evaluated by surface plasmon resonance (SPR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The viability evaluation was assessed by the tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) protocol in the fibroblast L929 line and a high level of biocompatibility, confirmed by SEM results, was found.

Efficacy of ceramides and niacinamide-containing moisturizer versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris: A split face, double-blinded, randomized controlled trial.

Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.

Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers

Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood–brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system. In this study, we investigated the biophysical properties of dendrimers and their complexes with siRNA directed against the apolipoprotein E (APOE) gene to identify an appropriate nanocarrier capable of safely delivering the cargo across the BBB. Our study yielded valuable insights into the complexation process, stability over time, the mechanisms of interaction, the influence of dendrimers on the oligonucleotide's spatial structure, and the potential cytotoxic effects on human cerebral microvascular endothelium cells. Based on our findings, we identified that the dendrimer G3Si PEG6000 was an optimal candidate for further research, potentially serving as a nanocarrier capable of safely delivering therapeutic agents across the BBB for the treatment of neurodegenerative disorders.

Discovery of novel 1,2,4-triazole tethered β-hydroxy sulfides as bacterial tyrosinase inhibitors: synthesis and biophysical evaluation through in vitro and in silico approaches.

In this study, a series of 1,2,4-triazole-tethered β-hydroxy sulfide scaffolds 11a-h was synthesized in good to remarkable yields (69-90%) through the thiolysis of oxiranes by the thiols in aqueous basic catalytic conditions. The synthesized 1,2,4-triazole-tethered β-hydroxy sulfides were screened against bacterial tyrosinase enzyme, and Gram-positive and Gram-negative bacterial cultures i.e., (S. aureus) Staphylococcus aureus & (E. coli) Escherichia coli. Among the synthesized derivatives, the molecules 11a (IC50 = 7.67 ± 1.00 μM), 11c (IC50 = 4.52 ± 0.09 μM), 11d (IC50 = 6.60 ± 1.25 μM), and 11f (IC50 = 5.93 ± 0.50 μM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC50 = 11.5 ± 1.00 μM) and kojic acid (IC50 = 30.34 ± 0.75 μM). The molecule benzofuran-triazol-propan-2-ol 11c proved to be the most potent bacterial tyrosinase inhibitory agent with a minimum IC50 of 4.52 ± 0.09 μM, as compared to other synthesized counterparts and both standards (kojic acid and ascorbic acid). The compound diphenyl-triazol-propan-2-ol 11a and benzofuran-triazole-propan-2-ol 11c showed comparable anti-bacterial chemotherapeutic efficacy with minimum inhibitory concentrations (MIC = 2.0 ± 2.25 mg mL-1 and 2.5 ± 0.00 mg mL-1, respectively) against S. aureus bacterial strain in comparison with standard antibiotic penicillin (MIC = 2.2 ± 1.15 mg mL-1). Furthermore, among the synthesized derivatives, only compound 11c demonstrated better anti-bacterial activity (MIC = 10 ± 0.40 mg mL-1) against E. coli, which was slightly less than the standard antibiotic i.e., penicillin (MIC = 2.4 ± 1.00 mg mL-1). The compound 11c demonstrated a better binding score (-7.08 kcal mol-1) than ascorbic acid (-5.59 kcal mol-1) and kojic acid (-5.78 kcal mol-1). Molecular docking studies also validate the in vitro anti-tyrosinase assay results; therefore, the molecule 11c can be the lead bacterial tyrosinase inhibitor as well as the antibacterial agent against both types of bacterial strains after suitable structural modifications.

Early Prediction of Hypertensive Diseases of Pregnancy by Using Combined Screening Methods in a Rural Population.

The most frequent medical issue during pregnancy is hypertension, which can complicate up to 10% to 15% of pregnancies worldwide. An estimated 14% of all maternal fatalities worldwide are thought to be caused by hypertensive disease of pregnancy, one of the main causes of maternal and fetal morbidity and mortality. Despite the fact that maternal mortality is substantially lower in high-income countries than in low- and middle-income countries, hypertension is still one of the leading causes of maternal death globally. Maternal mortality associated with hypertension fluctuated between 0.08 and 0.42 per 100,000 births between 2009 and 2015. In India, the estimated overall pooled prevalence of HDP was determined to be one out of 11 women, or 11% (95% CI, 5%-17%). Despite various government programs, there is still a high prevalence of hypertension, which calls for stakeholders and healthcare professionals to focus on providing both therapeutic and preventive care. The best solution is to concentrate more on the early detection of pregnancy-related hypertension and to guarantee its universal application so that proper care can be carried out to prevent maternal and fetal morbidity. To estimate the predictive value of the combination of maternal characteristics, i.e., mean arterial pressure (MAP), biophysical evaluation (uterine artery Doppler), and biochemical markers (pregnancy-associated plasma protein A (PAPP-A)), in the first trimester of pregnancy for hypertensive diseases of pregnancy. It was a prospective observational study of longitudinal variety thattook over 18 months in a tertiary care rural hospital. The number of women admitted to the hospital for labor care during 2019 was 5261. A total of 513 were diagnosed with hypertensive illnesses during pregnancy. At a prevalence rate of 10%, we calculated a sample size of 350 to achieve a sensitivity of 85% with an absolute error of 12.5% at a 95% CI. Maternal histories, such as age, education, socio-economic status, gravidity, and BMI, were taken along with three parameters, i.e., MAP, which was significant above 90 mmHg, uterine artery Doppler, which was taken significant above 1.69, and serum PAPP-A, which was significant at less than 0.69 ml/IU. We have found that the following are associated with theprediction of hypertension: among the maternal characteristics are advanced age >35 years, presence of body edema, and urine proteins along with MAP, uterine artery pulsatility index (UtA-PI), and PAPP-A are significant. The predictive accuracy of the combination of MAP, UtA-PI, and PAPP-A is also significant. We also found that there is a significant increase in cesarean sections and NICU admissions in hypertensive patients. A combination of screening parameters, including MAP, UtA-PI, and PAPP-A, to predict early hypertensive disease of pregnancy is developed and tested.

Biophysical evaluation of the effectiveness of high-frequency bipolar electric welding for closing defects in the dura mater in frontal sinus tumours with intracranial spread

One of the main tasks of surgical treatment of patients with frontal sinus neoplasms with intracranial spread is to seal the subdural space, which is achieved by hermetically connected dura mater. The purpose of this study was to investigate the structure of the tissues of the dura mater and dura mater-fascia junction using bipolar electric welding. The methods of light microscopy and infrared spectroscopy were used. When evaluating the results, no β-structured aggregates were observed in the tissue samples under study. There was minimal traumatic damage to the adjacent dura mater tissue and minimal thermal damage from vaporisation. Pacchioni granulations, venous pial, and cortical vessels of the dura mater were preserved. The study observed complete identity of the wave values of amide A, B, amide I, II spectra; preservation of amide A, B peaks. Preservation and curvature of the N-H arm and O =C-N band were changed within acceptable limits. The findings indicate the absence of β-structured protein aggregates in the junction area, which excludes the possibility of fibrous structures and, as a result, does not contribute to the formation of a meningeal scar. The structure of the collagen protein in the junction area is normal, altered but intact, with preservation of its functions. This indicates the feasibility of using the method of high-frequency bipolar electric welding for surgical closure of defects of the dura mater, as an alternative to closure with suture material

Principles and Applications of CF2X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery.

As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF2X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF2X moieties, we study their chemical/metabolic stability and their logP/solubility, as well as the role of XB in their small molecular crystal structures. Employing QM techniques, we analyze the observed interactions, provide insights into the conformational flexibilities and preferences in the potential interaction space. For their application in molecular design, we characterize their XB donor capacities and its interaction strength dependent on geometric parameters. Implementation of CF2X acetamides into our HEFLibs and biophysical evaluation (STD-NMR/ITC), followed by X-ray analysis, reveals a highly interesting binding mode for fragment 23 in JNK3, featuring an XB of CF2Br toward the P-loop, as well as chalcogen bonds. We suggest that underexplored chemical space combined with unconventional binding modes provides excellent opportunities for patentable chemotypes for therapeutic intervention.

Comparative assessment of 9-bromo noscapine ionic liquid and noscapine: Synthesis, in-vitro studies plus computational & biophysical evaluation with human hemoglobin

Noscapine is a proficient anticancer drug active against wide variety of tumors including lung cancer. Over time, several noscapine analogues have been assessed to maximize the efficiency of the drug, amongst which 9-bromo noscapine remains one of the most potent analogues till date. In the present work, we have synthesized 9-bromo noscapine ionic liquid [9-Br-Nos]IBr2, an active pharmaceutical ingredient based ionic liquid (API-IL) to address the existing issues of solubility and targeted drug delivery in the parent alkaloid as well as the synthesized analogues. We have devised a novel two-step synthesis route (first-ever ionic to ionic bromination) to obtain the desired [9-Br-Nos]IBr2 which is advantageous to its organic analogue in terms of increased solubility, lesser reaction time and better yield. Furthermore, we have compared 9-bromo noscapine ionic liquid with noscapine based on its binding interaction with human hemoglobin (Hb) studied via computational along with spectroscopic studies, and bioactivity against non-small cell lung cancer. We inferred formation of a complex between [9-Br-Nos]IBr2 and Hb in the stoichiometric ratio of 1:1, similar to noscapine. At 298 K, [9-Br-Nos]IBr2-Hb binding was found to exhibit Kb and ∆G of 36,307 M−1 and -11.5 KJmol−1, respectively, as compared to 159 M−1 and -12.5 KJmol−1 during Noscapine-Hb binding. This indicates a more stronger and viable interaction between [9-Br-Nos]IBr2 and Hb than the parent compound. From computational studies, the observed higher stability of [9-Br-Nos]I and better binding affinity with Hb with a binding energy of −91.75 kcalmol−1 supported the experimental observations. In the same light, novel [9-Br-Nos]IBr2 was found to exhibit an IC50 = 95.02 ± 6.32 μM compared to IC50 = 128.82 ± 2.87 μM for noscapine on A549 (non-small lung cancer) cell line at 48 h. Also, the desired ionic liquid proved to be more cytotoxic inducing a mortality rate of 87 % relative to 66 % evoked by noscapine at concentrations of 200 μM after 72 h.

Molecular Dynamics-Based Design and Biophysical Evaluation of Thermostable Single-Chain Fv Antibody Mutants Derived from Pharmaceutical Antibodies.

Antibody drugs are denatured under physical stress, e.g., friction, heat, and freezing, which triggers formation of aggregates and resultant allergic reactions. Design of a stable antibody is thus critical for the development of antibody drugs. Here, we obtained a thermostable single-chain Fv (scFv) antibody clone by rigidifying the flexible region. We first conducted a short molecular dynamics (MD) simulation (3 runs of 50 ns) to search for weak spots in the scFv antibody, i.e., flexible regions located outside the CDR (complementarity determining region) and the interface between the heavy-chain and light-chain variable regions. We then designed a thermostable mutant and evaluated it by means of a short MD simulation (3 runs of 50 ns) based on reductions in the root-mean-square fluctuation (RMSF) values and formation of new hydrophilic interactions around the weak spot. Finally, we designed the VL-R66G mutant by applying our strategy to scFv derived from trastuzumab. Trastuzumab scFv variants were prepared by using an Escherichia coli expression system, and the melting temperature-measured as a thermostability index-was 5 °C higher than that of the wild-type trastuzumab scFv, while the antigen-binding affinity was unchanged. Our strategy required few computational resources, and would be applicable to antibody drug discovery.

Analysis of Phytochemical content and Antioxidant activity of Mycelia sterilia isolated from Boerhaavia diffusa

Fungal endophytes are living asymptomatically inside the tissue of higher plants are of rising interest as they are the promising resource of bioactive agents. The current study shows that mycelia sterilia isolated from Boerhaavia diffusa would be a potent phytochemical and antioxidant source. The preliminary phytochemical analysis revealed the presence of different secondary metabolites and all the fungal extracts exhibited antioxidant activity. There was a positive association between the amount of phenol content and the antioxidant content of the fungal extracts. Further research needs to be done on isolating the active compound accountable for this free radical scavenging activity and biophysical evaluation will be carried out in the future.

Moisturizing emulsion with Attalea speciosa (babassu) oil as an alternative treatment for cutaneous xerosis in leprosy

This study investigated the moisturizing action of a topical emulsion containing babassu coconut almond oil in xerotic skin volunteers treated or undergoing leprosy treatment. A total of 20 volunteers (16 men and 4 women, with a mean age of 52.2 ± 15.3) with cutaneous xerosis performed the tests after signing the informed consent form. The research subjects were instructed to use the product under investigation (Attalea speciosa almond oil gel-cream formulation) 1 (one) once a day, in two 15-day cycles: first with the gel-cream formulation with babassu oil (treatment A) and the second with the gel-cream formulation without babassu oil (treatment B). The moisturizing emulsion did not significantly alter (p> 0.05) the xerotic skin pH of the volunteers, treatment A (11.6 ± 0.1), treatment B (8.8 ± 0.2) and control (11.4 ± 0.2) at week W7, when compared to week W15, treatment A (11.0 ± 0.4), treatment B (11.6 ± 0.1) and control (11.4 ± 0.2). Clinical evaluations showed the efficacy and good tolerability of topical emulsion in the hydration of xerotic skin. The biophysical evaluation of the moisturizing emulsion proved the significant improvement of skin moisture.

Computational Design, Synthesis, and Biophysical Evaluation of β-Amido Boronic Acids as SARS-CoV-2 Mpro Inhibitors.

The COVID-19 pandemic has given a strong impetus to the search for antivirals active on SARS-associated coronaviruses. Over these years, numerous vaccines have been developed and many of these are effective and clinically available. Similarly, small molecules and monoclonal antibodies have also been approved by the FDA and EMA for the treatment of SARS-CoV-2 infection in patients who could develop the severe form of COVID-19. Among the available therapeutic tools, the small molecule nirmatrelvir was approved in 2021. It is a drug capable of binding to the Mpro protease, an enzyme encoded by the viral genome and essential for viral intracellular replication. In this work, by virtual screening of a focused library of β-amido boronic acids, we have designed and synthesized a focused library of compounds. All of them were biophysically tested by microscale thermophoresis, attaining encouraging results. Moreover, they also displayed Mpro protease inhibitory activity, as demonstrated by performing enzymatic assays. We are confident that this study will pave the way for the design of new drugs potentially useful for the treatment of SARS-CoV-2 viral infection.

Identification of New L-Fucosyl and L-Galactosyl Amides as Glycomimetic Ligands of TNF Lectin Domain of BC2L-C from Burkholderia cenocepacia.

The inhibition of carbohydrate-lectin interactions is being explored as an efficient approach to anti adhesion therapy and biofilm destabilization, two alternative antimicrobial strategies that are being explored against resistant pathogens. BC2L-C is a new type of lectin from Burkholderia cenocepacia that binds (mammalian) fucosides at the N-terminal domain and (bacterial) mannosides at the C-terminal domain. This double carbohydrate specificity allows the lectin to crosslink host cells and bacterial cells. We have recently reported the design and generation of the first glycomimetic antagonists of BC2L-C, β-C- or β-N-fucosides that target the fucose-specific N-terminal domain (BC2L-C-Nt). The low water solubility of the designed N-fucosides prevented a full examination of this promising series of ligands. In this work, we describe the synthesis and biophysical evaluation of new L-fucosyl and L-galactosyl amides, designed to be water soluble and to interact with BC2L-C-Nt. The protein-ligand interaction was investigated by Saturation Transfer Difference NMR, Isothermal Titration Calorimetry and crystallographic studies. STD-NMR experiments showed that both fucosyl and galactosyl amides compete with α-methyl fucoside for lectin binding. A new hit compound was identified with good water solubility and an affinity for BC2L-C-Nt of 159 μM (ITC), which represents a one order of magnitude gain over α-methyl fucoside. The x-ray structure of its complex with BC2L-C-Nt was solved at 1.55 Å resolution.

Biophysical evaluation of the oligomerization and conformational properties of the N-terminal domain of TDP-43

TDP-43 is an RNA-binding protein that presents four domains comprising an N-terminal region, two RNA recognition motifs and a C-terminal region. The N-terminal domain (NTD) has a relevant role in the oligomerization and splicing activity of TDP-43. In this work, we have expressed, purified and biophysically characterized the region that includes residues 1 to 102 that contains the nuclear localization signal (residues 80–102, NLS). Furthermore, we have evaluated the oligomerization equilibrium for this protein fragment. Also, we have determined changes in the tertiary structure and its stability in a broad range of pH values by means of different spectroscopic methods. Additionally, we compared this fragment with the one that lacks the NLS employing experimental and computational methods. Finally, we evaluated the motion of dimeric forms to get insights into the conformational flexibility of this TDP-43 module in an oligomeric state. Our results suggest that this domain has a conformational plasticity in the vicinity of the single tryptophan of this domain (Trp68), which is enhanced by the presence of the nuclear localization signal. All these results help to understand the molecular features of the NTD of TDP-43.

Biophysical Evaluation of Small Molecules Potentially Targeting NSP10 by Surface Plasmon Resonance

Biophysical Evaluation of Small Molecules Potentially Targeting NSP10 by Surface Plasmon Resonance

Neutraligands of C5a can potentially occlude the interaction of C5a with the complement receptors C5aR1 and C5aR2.

The complement system is central to the rapid immune response witnessed in vertebrates and invertebrates, which plays a crucial role in physiology and pathophysiology. Complement activation fuels the proteolytic cascade, which produces several complement fragments that interacts with a distinct set of complement receptors. Among all the complement fragments, C5a is one of the most potent anaphylatoxins, which exerts solid pro-inflammatory responses in a myriad of tissues by binding to the complement receptors such as C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2), whichare part of the rhodopsin subfamily of G-protein coupled receptors. In terms of signaling cascade, recruitment of C5aR1 or C5aR2 by C5a triggers the association of either G-proteins or β-arrestins, providing a protective response under normal physiological conditions and a destructive response under pathophysiological conditions. As a result, both deficiency and unregulated activation of the complement lead to clinical conditions that require therapeutic intervention. Indeed, complement therapeutics targeting either the complement fragments or the complement receptors are being actively pursued by both industry and academia. In this context, the model structural complex of C5a-C5aR1 interactions, followed by a biophysical evaluation of the model complex, has been elaborated on earlier. In addition, through the drug repurposing strategy, we have shown that small molecule drugs such asraloxifene and prednisone may act as neutraligands of C5a by effectively binding to C5a and altering its biologically active molecular conformation. Very recently, structural models illustrating the intermolecular interaction of C5a with C5aR2 have also been elaborated by our group. In the current study, we provide the biophysical validation of the C5a-C5aR2 model complex by recruiting major synthetic peptide fragments of C5aR2 against C5a. In addition, the ability of the selected neutraligands to hinder the interaction of C5a with the peptide fragments derived from both C5aR1 and C5aR2 has also been explored. Overall, the computational and experimental data provided in the current study supports the idea that small molecule drugs targeting C5a can potentially neutralize C5a's ability to interact effectively with its cognate complement receptors, which can be beneficial in modulating the destructive signaling response of C5a under pathological conditions.

Biophysical Evaluation of Water-Soluble Curcumin Encapsulated in β-Cyclodextrins on Colorectal Cancer Cells.

Curcumin (CUR), a curcuminoid originating from turmeric root, possesses diverse pharmacological applications, including potent anticancer properties. However, the use of this efficacious agent in cancer therapy has been limited due to low water solubility and poor bioavailability. To overcome these problems, a drug delivery system was established as an excipient allowing improved dispersion in aqueous media coupled with enhanced in vitro anticancer effects. Different analyses such as UV-vis spectroscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), solubility and dissolution assays were determined to monitor the successful encapsulation of CUR within the inner cavity of a β-cyclodextrin (β-CD) complex. The results indicated that water solubility was improved by 205.75-fold compared to pure CUR. Based on cytotoxicity data obtained from MTT assays, the inclusion complex exhibited a greater decrease in cancer cell viability compared to pure CUR. Moreover, cancer cell migration rates were decreased by 75.5% and 38.92%, invasion rates were decreased by 37.7% and 35.7%, while apoptosis rates were increased by 26.3% and 14.2%, and both caused caspase 3 activation toward colorectal cancer cells (SW480 and HCT116 cells). This efficacious formulation that enables improved aqueous dispersion is potentially useful and can be extended for various chemotherapeutic applications. Preliminary toxicity evaluation also indicated that its composition can be safely used in humans for cancer therapy.