Comparison of the effect of different doses of phenylephrine infusion on the prevention of hypotension in the elderly under spinal anaesthesia in orthopaedic surgery.

BACKGROUND: Considering the vasopressor drug categories and doses that can be used for elderly patients following hypotension are few, the present trial aimed to compare the effect of different doses of phenylephrine infusion on the prevention of hypotension in elderly patients undergoing orthopaedic lower extremities surgery. METHODS: This randomised, double-blind prospective clinical trial was conducted by including 60 elderly patients older than 60 years and classified as American Society of Anesthesiology class I and II who were candidates for femur fracture fixation surgery. White and black cards randomly allocated patients to: group A (25µg/kg/h phenylephrine) or group B (35µg/kg/h phenylephrine). RESULTS: At the T3-T7 time points, group A's systolic and diastolic blood pressure was significantly higher than in group B's (p < 0.05). However, after 27 minutes (T0-T7) of phenylephrine infusion, statistical analysis showed no significant difference between the two groups regarding blood pressure (T8-Tend). The frequency of bradycardia and reactive hypertension in group B were significantly higher than in group A (p = 0.02) and (p = 0.03), respectively. There was no significant difference between the bleeding loss, blood transfusion and crystalloid volume in both groups (p > 0.05). CONCLUSION: Our trial illustrated that high-dose phenylephrine infusion could not assure haemodynamic stability and may cause some side effects.

Biologically based strategies for overcoming in vivo barriers with functional nano-delivery systems.

Nanomedicine has been developed to reduce or eliminate the side effects and toxicity upon systemic therapy of chemotherapeutic agents and to improve their therapeutic efficacy. However, the translation of non-sized or nano-encapsulated drugs is hampered by the low penetration and accumulation of engineered nanoparticles (NPs) in sites of tumors as well as their poor pharmacokinetics. This may be due to the synthetic structure of NPs and also complicated and unknown characteristics of the solid tumor microenvironment (TME). As a result, the TME is being better identified, and the interactions between NPs and the TME or human body are being discovered or predicted. These findings have led to the development of more biocompatible, intelligent, and controllable bio-based nanoformulations that could overcome current barriers and provide sufficient drug delivery to the TME, as discussed in this paper. These formulations are designed to (i) modify the surface of NPs to improve blood circulation while reducing their off-target accumulation and side effects in vivo, (ii) pass through the tumor vasculature by modulating or targeting angiogenesis, (iii) promote NPs distribution in solid tumor regions by applying biological/physical stimuli or extracellular matrix remodeling, and (iv) overcome the cell membrane barrier and other compartments of the cell by specific cell targeting to release the payload drug into the cytoplasm or nucleoplasm.

Exploring the detailed role of interleukins in cancer: A comprehensive review of literature.

The cancer cells that are not normal can grow into tumors, invade surrounding tissues, and travel to other parts of the body via the lymphatic or circulatory systems. Interleukins, a vital class of signaling proteins, facilitate cell-to-cell contact within the immune system. A type of non-coding RNA known as lncRNAs mediates its actions by regulating miRNA-mRNA roles (Interleukins). Because of their dual function in controlling the growth of tumors and altering the immune system's response to cancer cells, interleukins have been extensively studied concerning cancer. Understanding the complex relationships between interleukins, the immune system, the tumor microenvironment, and the components of interleukin signaling pathways that impact the miRNA-mRNA axis, including lncRNAs, has advanced significantly in cancer research. Due to the significant and all-encompassing influence of interleukins on the immune system and the development and advancement of cancers, lncRNAs play a crucial role in cancer research by modulating interleukins. Their diverse effects on immune system regulation, tumor growth encouragement, and tumor inhibition make them appealing candidates for potential cancer treatments and diagnostics. A deeper understanding of the relationship between the biology of interleukin and lncRNAs will likely result in more effective immunotherapy strategies and individualized cancer treatments.

Performance of ginger constituents against SARS-CoV-2 virus: A therapeutic and theoretical approach.

In the present research, ginger extracted compounds, namely; Gingerol {(1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone} (1), Zingerone {(4-(4-Hydroxy-3-methoxyphenyl)-2-butanone)} (2), and Shogoals {(E)-1-(4-Hydroxy-3- methoxyphenyl) dec-4-en-3-one)} (3) have been investigated as SARS-Cov-2 inhibitors. The interaction of extracted compounds with the virus's spikes may restrict the virus's reproduction or give time to the body's immune system to detect viruses, consequently producing appropriate antibodies. Gaussian 09 with a 6-311G (d, p) basis set, UCA FUKUI, MGL implement, DSV, and LigPlus software were utilized. The active sites for adsorption were identified using the total electron density (TED), FUKUI function, and Millikan charges. Furthermore, docking analysis clearly showed that the inhibition of viral replication depends on binding energy (Eb) and ligand efficiency (LE). A docking study revealed that the inhibition ability of the studied compounds on SARS-CoV-2 was in the order of 2 > 3 > 1.

A comprehensive review of lncRNA CRNDE in cancer progression and pathology, with a specific glance at the epithelial-mesenchymal transition (EMT) process.

It has been suggested that the long non-coding RNAs (lncRNAs), such as colorectal neoplasia differentially expressed (CRNDE), may contribute to the formation of human cancer. It is yet unknown, though, what therapeutic significance CRNDE expression has for different forms of cancer. CRNDE has recently been proposed as a possible diagnostic biomarker and prognostic pred for excellent specificity and sensitivity in cancer tissues and plasma. To provide the groundwork for potential future therapeutic uses of CRNDE, we briefly overview its biological action and related cancer-related pathways. Next, we mainly address the impact of CRNDE on the epithelial-mesenchymal transition (EMT). The epithelial-mesenchymal transition, or EMT, is an essential biological mechanism involved in the spread of cancer.

Overcoming drug resistance with specific nano scales to targeted therapy: Focused on metastatic cancers.

Metastatic cancer, which accounts for the majority of cancer fatalities, is a difficult illness to treat. Currently used cancer treatments include radiation therapy, chemotherapy, surgery, and targeted treatment (immune, gene, and hormonal). The disadvantages of these treatments include a high risk of tumor recurrence and surgical complications that may result in permanent deformities. On the other hand, most chemotherapy drugs are small molecules, which usually have unfavorable side effects, low absorption, poor selectivity, and multi-drug resistance. Anticancer drugs can be delivered precisely to the cancer spot by encapsulating them to reduce side effects. Stimuli-responsive nanocarriers can be used for drug release at cancer sites and provide target-specific delivery. As previously stated, metastasis is the primary cause of cancer-related mortality. We have evaluated the usage of nano-medications in the treatment of some metastatic tumors.

Novel and potential therapy options for a range of cancer diseases: Using Flavonoid.

Cancer is a complex group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. These abnormal cells can form tumors or invade nearby tissues and organs, leading to a range of health problems. There are many different types of cancer, which can be categorized based on the location of the primary tumor, the type of cell involved, and the stage of the disease. Some common types of cancer include breast cancer, lung cancer, colon cancer, prostate cancer, and skin cancer. Nanoparticles are very small particles, typically ranging in size from 1 to 100 nanometers, that have unique physical and chemical properties. These properties make them attractive for use in a variety of applications, including cancer treatment. Flavonoids, which are natural compounds found in fruits, vegetables, and other plant-based foods, have been extensively studied for their potential role in cancer prevention and treatment. Flavonoids have been shown to possess a wide range of biological activities, including antioxidant, anti-inflammatory, anti-cancer, and anti-metastatic effects.

Correction: Immobilized Ni on TMEDA@ßSiO2@αSiO2@Fe3O4: as a novel magnetic nanocatalyst for preparation of pyrido[2,3-d:6,5-d']dipyrimidines.

[This corrects the article DOI: 10.1039/D3RA01720F.].

Dosimetric properties of PASSAG polymer gel dosimeter in electron beam radiotherapy using magnetic resonance imaging.

BACKGROUND: Several physical factors such as photon beam energy, electron beam energy, and dose rate may affect the dosimetric properties of polymer gel dosimeters. The photon beam energy and dose rate dependence of PASSAG gel dosimeter were previously evaluated. OBJECTIVE: This study aims to assess the dosimetric properties of the optimized PASSAG gel samples in various electron beam energies. METHODS: The optimized PASSAG gel samples are first fabricated and irradiated to various electron energies (5, 7, 10 and 12 MeV). Then, the response (R2) and sensitivity of gel samples are analyzed by magnetic resonance imaging technique at a dose range of 0 to 10 Gy, scanning room temperature range of 15 to 22 °C, and post-irradiation time range of 1 to 30 days. RESULTS: The R2-dose response and sensitivity of gel samples do not change under the evaluated electron beam energies (the differences are less than 5%). Furthermore, a dose resolution range of 11 to 38 cGy is obtained for the gel samples irradiated to different electron beam energies. Moreover, the findings show that the R2-dose response and sensitivity dependence of gel samples on electron beam energy varies over different scanning room temperatures and post-irradiation times. CONCLUSION: The dosimetric assessment of the optimized PASSAG gel samples provides the promising data for this dosimeter during electron beam radiotherapy.

Immobilized Ni on TMEDA@ßSiO2@αSiO2@Fe3O4: as a novel magnetic nanocatalyst for preparation of pyrido[2,3-d:6,5-d']dipyrimidines.

In the current body of research, a very quick and effectual procedure for the synthesis of pyrido[2,3-d:6,5-d']dipyrimidines has been developed. This method is accomplished through the one-pot multi-component reaction of 2-thiobarbituric acid, NH4OAc and aldehydes utilizing Ni-TMEDA@ßSiO2@αSiO2@Fe3O4 as a novel mesoporous nanomagnetic catalyst at room temperature. This protocol is one of the few reports of the preparation of these derivatives without the use of conventional heating as well as energies such as microwave and ultrasound radiation. The characterization of the prepared catalyst was well accomplished by different techniques such as FT-IR, ICP-OES, SEM, TEM, BET, XRD, VSM, TGA, EDX and Elemental mapping. This organometallic catalyst was reusable for seven times with negligible decrement in its catalytic performance. In addition, all of the products were produced with high TON and TOF values, which demonstrates that our catalyst has a very high level of activity in the preparation of pyrido[2,3-d:6,5-d']dipyrimidines.

Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs.

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes in tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of NF-κB promotes carcinogenesis, including increased proliferation, invasion, and therapy resistance. As an incurable disease globally, prostate cancer is a significant health concern, and research into genetic mutations and NF-κB function has the efficacy to facilitate the introduction of novel therapies. NF-κB upregulation is observed during prostate cancer progression, resulting in increased cell cycle progression and proliferation rates. Additionally, NF-κB endorses resistance to cell death and enhances the capacity for metastasis, particularly bone metastasis. Overexpression of NF-κB triggers chemoresistance and radio-resistance, and inhibition of NF-κB by anti-tumor compounds can reduce cancer progression. Interestingly, non-coding RNA transcripts can regulate NF-κB level and its nuclear transfer, offering a potential avenue for modulating prostate cancer progression.

Evaluation of a biosensor-based graphene oxide-DNA nanohybrid for lung cancer.

Lung cancer is nowadays among the most prevalent diseases worldwide and features the highest mortality rate among various cancers, indicating that early diagnosis of the disease is of paramount importance. Given that the conventional methods of cancer detection are expensive and time-consuming, special attention has been paid to the provision of less expensive and faster techniques. In recent years, the dramatic advances in nanotechnology and the development of various nanomaterials have led to activities in this context. Recent studies indicate that the graphene oxide (GO) nanomaterial has high potential in the design of nano biosensors for lung cancer detection owing to its unique properties. In the current article, a nano biosensor based on a DNA-GO nanohybrid is introduced to detect deletion mutations causing lung cancer. In this method, mutations were detected using a FAM-labeled DNA probe with fluorescence spectrometry. GO was synthesized according to Hummers' method and examined and confirmed using Fourier Transform Infrared (FT-IR) Spectrometry and UV-vis spectrometry methods and Transmission Electron Microscopy (TEM) images.

The emerging crosstalk between atherosclerosis-related microRNAs and Bermuda triangle of foam cells: Cholesterol influx, trafficking, and efflux.

In atherosclerosis, the gradual buildup of lipid particles into the sub-endothelium of damaged arteries leads to numerous lipid alterations. The absorption of these modified lipids by monocyte-derived macrophages in the arterial wall leads to cholesterol accumulation and increases the likelihood of foam cell formation and fatty streak, which is an early characteristic of atherosclerosis. Foam cell formation is related to an imbalance in cholesterol influx, trafficking, and efflux. The formation of foam cells is heavily regulated by various mechanisms, among them, the role of epigenetic factors like microRNA alteration in the formation of foam cells has been well studied. Recent studies have focused on the potential interplay between microRNAs and foam cell formation in the pathogenesis of atherosclerosis; nevertheless, there is significant space to progress in this attractive field. This review has focused to examine the underlying processes of foam cell formation and microRNA crosstalk to provide a deep insight into therapeutic implications in atherosclerosis.

Development and Evaluation of Biocompatible Topical Petrolatum-liquid Crystal Formulations with Enhanced Skin Permeation Properties.

Transdermal administration represents a major advancement over traditional pharmaceutical dosing methods. However, a frequent issue is inadequate penetration of the active medicinal component through the skin. As a result, in the current research, we assessed the utility of newly developed petrolatum-liquid crystal (LC) ointment formulations and characterized their biocompatibility and function in the transdermal drug delivery system. To begin, we made petrolatum-LC formulations using p-aminobenzoic acid (PABA) as a hydrophilic model molecule. The viscosity, small-angle X-ray scattering (SAXS), particle diameters, and z-potential were measured to assess the physicochemical properties of the formulations. A dialysis release technique was used to evaluate medication release from petrolatum-LC formulations. In vitro testing was performed to determine the potential to enhance skin penetration. The biocompatibility of the produced formulations was further tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and single-cell gel electrophoresis. According to the results, the novel petrolatum-LC formulations are biocompatible and effective in forming hexosomes. PABA skin penetration was significantly enhanced by the new petrolatum-LC formulations. According to this study, petroleum-LC formulations are more efficient than commercial petrolatum in terms of skin permeability improvement and PABA skin concentration.

Inhibition of SARS-CoV-2 reproduction using Boswellia carterii: A theoretical study.

This study investigated the possibility of inhibition of the SARS-CoV-2 virus using the compounds alpha-Boswellic acid (ABA) and beta-Boswellic acid (BBA) which are active components in the well-known natural product Boswellia carterii (BC). The SARS-CoV-2 virus reproduces in the body by linking its spike with the cell receptor. At the same time, a pH range (4.5-6) of the cell's lysosomes is considered as a perfect environment to release RNA in the cell cytoplasm. In view of these, docking studies were employed to study the interaction between the spikes of the virus and ABA or BBA using Molecular Graphic Laboratory (MGL) tools and AutoDock Vina application. The binding of the ABA and BBA with the spike of the virus could inhibit its reproduction or provide sufficient time for the immune system to recognize the virus and hence, produce suitable antibodies. In addition, the pKa of ABA, BBA and hydroxychloroquine (HCQ) were calculated using HF/6-311G (d,p) method and then they were compared with the experimental pKa of HCQ. The Lethal Concentrations (LC50) of ABA and BBA were also calculated. In addition, molecular electrostatic potential is reported which indicates the active sites of ABA and BBA.

Establishment of an evaluation method to detect drug distribution in hair follicles.

Development of an appropriate method to evaluate drug disposition or targeting ability in hair follicles (HFs) is urgently needed in order to develop useful pharmaceutical products with pharmacological effects in HFs. In the present study, a cyanoacrylate biopsy (CB) method was used to measure drug disposition in HFs using a model hydrophilic drug, caffeine (CAF), and a lipophilic drug, 4-butylresorcinol (BR), in excised porcine skin. As a result, the height of HF replicas and the recovery ratio decreased with an increase in the application times of the CB method. HF replicas with a length of approximately 175 µm were obtained using a single application of the CB method. Drug distribution in the HF was detected even 5 min after topical application regardless of the lipophilicity of the drugs, although no drug disposition was observed in the deeper layers of the stratum corneum at the same time (5 min). Furthermore, significantly higher amounts of BR were observed in the stratum corneum and HF, compared with those of CAF. These results suggested that the CB method could be useful to evaluate the safety and efficacy as well as the disposition of topically applied chemicals, especially for HF-targeting drugs.

Development and Optimization of Orally and Topically Applied Liquid Crystal Drug Formulations.

Liquid crystal (LC)-forming lipids represent an important class of biocompatible amphiphiles and their application extends to cosmeceutical, dietary, and pharmaceutical technologies. In the present study, we aimed to develop strategies for designing and optimizing oral and topical LC formulations by evaluating their in vitro and in vivo drug absorption performances. C17-Monoglycerol ester (MGE) was used as a LC-forming lipid. p-Amino benzoic acid, methyl PABA, ethyl PABA, and sodium fluorescein were selected as drug models with different physiochemical properties. Various oral and topical LC formulations were designed based on changes in the LC forming lipid contents in the formulations and entrapped with different physiochemical properties of the drugs. The LC phase structures were evaluated using small-angle X-ray scattering (SAXS). The drug-release profiles from LC formulations were determined using a dialysis membrane method. In vivo oral absorption of LC formulations was conducted in Wistar rats. Furthermore, the skin penetration of drugs from LC formulations was investigated by in vitro skin permeation studies. As a result, although the release profile was influenced by changes in MGE concentration, it was more dramatically influenced by changes in the physiochemical properties of the entrapped drugs. Drug absorption after oral and topical administration of LC formulations was dramatically affected by the concentration of MGE. The concentration of LC-forming lipid and the physiochemical properties of entrapped drugs are key issues for good performance of the LC formulations in various pharmaceutical applications. The present results could enable researchers to manipulate LC formulation approaches intended to improve the oral absorption and skin permeation of drugs.

A Novel Chemical Enhancer Approach for Transdermal Drug Delivery with C17-Monoglycerol Ester Liquid Crystal-forming Lipid.

Transdermal administration of drugs represents an excellent alternative to conventional pharmaceutical dosage forms. However, insufficient penetration of the active pharmaceutical substance through the skin is a common problem. Thus, in the present study we evaluated the skin permeation enhancing ability of liquid crystal (LC) topical formulations. A recently developed LC-forming lipid, C17- monoglycerol ester (MGE), was evaluated and compared with glycerol monoolate (GMO), which is considered as the gold standard for LC formulations. We initially prepared LC formulations containing drugs with different physiochemical properties (tranexamic acid [TXA], 4-methoxy-salicylic acid [4-MS], catechin [CC], and calcein [Cal]), and confirmed the LC phase structures in the prepared formulations using a polarizing light microscope and a small-angle X-ray scattering (SAXS). The physicochemical properties of these formulations were also assessed using a viscometer and a zetasizer. The release rate of the drugs from the LC formulations was determined using a dialysis release method. The skin penetration-enhancing ability of LC formulations was also investigated in an in vitro skin permeation study. The results showed that both MGE- and GMO-LC-forming lipids shared the same behavior in terms of their birefringence indexes, LC phase structures, particle sizes, and zeta potentials. Both the MGE- and GMO-LC formulations managed to improve the skin permeation for various drugs with a range of physiochemical properties. However, MGE formulations showed lower viscosity, faster drug release rate, and better skin penetration-enhancing ability than GMO formulations, strongly suggesting that the low viscosity of MGELC-forming lipids might influence drug diffusivity and permeability through the skin. The present MGELC formulation might be utilized as a promising new topical formulation for therapeutic drugs and cosmetic ingredients.

Usefulness of liquid-crystal oral formulations to enhance the bioavailability and skin tissue targeting of p-amino benzoic acid as a model compound.

Topical formulations are not always suitable to deliver active ingredients to large areas of skin. Thus, in this study, we aimed to develop an oral formulation for skin tissue targeting with a high bioavailability using liquid crystal (LC) dispersions comprising cubosomes of a mal-absorptive model compound, p-amino benzoic acid (PABA), which is an active element in cosmeceuticals, dietary supplements and skin disorder medicines. The bioavailability and skin concentration of PABA were investigated after oral administration in rats. The effect of the remaining amount of the LC formulation in the stomach on the pharmacokinetic profiles of orally administered PABA was evaluated. The skin permeation and concentration of PABA were also investigated using an in vitro permeation experiment. As a result, the bioavailability of PABA was significantly improved by administration of PABA-LC formulations compared with PABA solution alone, although the effect was greatly influenced by the type of LC-forming lipids. The in vitro skin permeation study showed that the PABA concentration in the skin when applied from the dermis side was higher than when applied from the epidermis side. These findings suggested that oral administration advantageously supports skin targeting, and oral LC formulations could be a promising material in cosmeceutical, dietary and clinical fields.

In Silico Estimation of Skin Concentration Following the Dermal Exposure to Chemicals.

PURPOSE: To develop an in silico method based on Fick's law of diffusion to estimate the skin concentration following dermal exposure to chemicals with a wide range of lipophilicity. METHODS: Permeation experiments of various chemicals were performed through rat and porcine skin. Permeation parameters, namely, permeability coefficient and partition coefficient, were obtained by the fitting of data to two-layered and one-layered diffusion models for whole and stripped skin. The mean skin concentration of chemicals during steady-state permeation was calculated using the permeation parameters and compared with the observed values. RESULTS: All permeation profiles could be described by the diffusion models. The estimated skin concentrations of chemicals using permeation parameters were close to the observed levels and most data fell within the 95% confidence interval for complete prediction. The permeability coefficient and partition coefficient for stripped skin were almost constant, being independent of the permeant's lipophilicity. CONCLUSIONS: Skin concentration following dermal exposure to various chemicals can be accurately estimated based on Fick's law of diffusion. This method should become a useful tool to assess the efficacy of topically applied drugs and cosmetic ingredients, as well as the risk of chemicals likely to cause skin disorders and diseases.