Pharmaceutical Sciences
Volume:28 Issue: 1, Jan 2022

Ras proteins are considered as one of the most critical cancer initiators. Mutations of this protein family lead to the continuous activation of the proliferation pathways. Therefore, many efforts have been taken to design the anti-mutant Ras drug candidates. Regardless of the development of promising inhibitors of Ras G12C mutant in a specific cancer type, there is no approved inhibitor of Ras mutants in the clinic. One of the significant limitations is to inhibit particular mutants and not to affect the wild-type Ras variants. Here we present a review on the mechanism of action of the Ras proteins to get a better insight into the strategies utilized to inhibit Ras-mutated cancers. The direct Ras inhibition strategies are then highlighted to obtain a better perspective of possible promising approaches to target Ras proteins in cancer therapy

Breast cancer screening tests could reduce the mortality rates for breast cancer patients. Screening and detection are the keystone of cancer prevention and may significantly minimize the death rates in breast cancer patients for long-term. In this review, we would like to present a comprehensive summary from recent publications of the current development for breast cancer screening, classification of breast cancer based on pathological diagnosis, as well as development of breast cancer detection.

The sources of the articles were collected from research published in the PubMed, NCBI databases and manual searches without time restriction based on review of the title, abstract and full review of the articles, using the keywords “breast cancer”, “diagnostic”, “screening”, “imaging”, “biomarker” and the combination of these terms. The criteria excluded in selecting references were articles that are not written in English, newspapers, and posters.

Of the 146 articles that were selected, there were 103 articles included. Breast cancer screening consists of imaging and pathological assessment such as invasive biopsies of tumor tissue and measurement of biomarkers. The recent development of breast cancer screening utilizing different models and methods like biomarkers were being reviewed. For imaging methods, there are mammography, digital breast tomosynthesis (3D mammography), magnetic resonance imaging (MRI), and ultrasonography. For pathological assessment, there are primary biomarker analysis for breast cancer (estrogen receptor, progesterone receptor, HER2, KI67 index) and liquid biomarker analysis from blood or saliva samples. Additionally, there are some diagnostic kit models for breast cancer screening that were in use such as NanoString nCounter®, MammaTyper®, CellSearch System™, and AdnaTest BreastCancer™.

Each of these methods has its own limitations. Therefore, the development of breast cancer models should be more sensitive, reliable, approachable and less harmful.

Nicolau syndrome, although it is quite rare, often occurs following intramuscular injections of different medications, especially diclofenac and penicillins. Accordingly, its symptoms usually begin with severe pain during injection, leading to ulceration and necrosis of the local tissue over time. Immediate diagnosis and treatment in the case of this syndrome, are of great importance. There are no established criteria for Nicolau’s diagnosis, and preferably, these can be achieved by examining the patient’s symptoms and eliminating differential diagnoses. The proposed treatments are primarily symptomatic therapy and measures such as fasciotomy, debridement, and plastic surgery provided in the affected area. The exact cause of this syndrome has not been determined yet. However, since vasospasm, thrombosis, and embolism have been observed in most of Nicolau syndrome cases, so any intra-arterial/para-arterial injection or any other factor leading to these three conditions could be hypothetically regarded as the cause of this problem. This review aims to provide a comprehensive overview of Nicolau’s symptoms, diagnosis, treatment methods, and prevention. It also investigates the association between the incidence of this disease and some factors such as gender, age, injection method, and causative drugs, in order to widen our understanding on this syndrome and help practitioners with a much faster diagnosis method and step-by-step approach to Nicolau syndrome.

Iodinated contrast agents are commonly used in diagnostic radiography techniques along with therapeutic interventions. Contrast-Induced Acute Kidney Injury (CI-AKI) is a significant problem of all angiographic procedures, triggered by the use of Iodinated Contrast Media (ICM). There are conflicting data concerning the prevention and treatment of CIAKI. Numerous approaches have been studied to prevent CI-AKI, but the therapy of choice remains undetermined. The cornerstones of CI-AKI prevention include low-osmolar ICM and intravenous hydration. The recommended hydration must be achieved by means of an isotonic solution of saline. Statins were tested against AKI due to their anti-inflammatory action and antioxidant effect on endothelial function. Novel approaches are required to investigate the short-term effects of high dosage atorvastatin versus sodium bicarbonate on CI-AKI prevention. The objective of this review is to compare the findings of various studies that had applied different doses of statins, sodium bicarbonate, and other agents for preventing CI-AKI.

Newbouldia laevis (P. Beauv.) Seem. (Family, Bignoniaceae), commonly known as tree of life, is a purple-flowering plant that is widely distributed in many parts of Africa. Different parts of the plant, including the leaves, flower, stems and roots are prevalently used in African traditional medicine for the management of many diseases and conditions like diabetes, hypertension, skin diseases, ulcer, tumors, pains, infectious diseases, inflammation, dysentery, sickle celldisease and impotency. This review discusses the trado-medical uses, chemical constituents, and biological activities of N. laevis. Based on information generated from scientific investigations deposited in PubMed and SCOPUS, the chemical constituents of the plant include glycosides, anthraquinolones, volatile oils, tannins, steroids, alkaloids, flavonoids, terpenoids and sterols. Extracts prepared from different parts of the plant of the plant and compounds isolated from them have been reported to have several health-promoting potentials such as antioxidant, antimalarial, trypanocidal, antimicrobial, anthelmintic, analgesic, anti-inflammatory, antidiabetic, antiarthritic,anti-thrombotic, cytoprotective, anti-hypertensive, central nervous system modulatory, male reproduction enhancing and oxytocic properties. These scientific investigations have led credence to the ethnobotanical uses of the plant in folkloric practice. In addition, the presence of phytochemical constituents in the plant might be responsible for the wide biological potentials.

Tamoxifen (TAM) is the main treatment of estrogen receptor (ER)-positive breast cancer, however; its adverse effects and development of resistance hinder its use. Concanavalin A (Con A) is a mannose/glucose-binding lectin that has been reported to induce apoptosis in a variety of cell lines.

The effects of Con A on TAM-induced cell death in ERα positive cell line (MCF-7) were elucidated to identify the potential underlying molecular mechanisms using in silico (molecular docking) and in vitro (cytotoxicity assay, cell cycle analysis, annexin V-FITC apoptosis assay, and reverse transcription and quantitative real time-PCR) techniques as well.

The results demonstrated that combined treatment with Con A and TAM reduced the expression of ERα, which showed clear synergistic effects on inhibiting the cell viability of MCF- 7 cells. Interestingly, the combined treatment induces G1 phase arrest and reduces cyclin D1 activity while increasing apoptosis and autophagy as indicated by decreasing the expression level of anti-apoptosis gene BCl-2 and increased apoptosis/autophagic gene BNIP3. Molecular docking was conducted to evaluate the binding affinity of Con A towards ERα, and it revealed its potential activity as an ERα antagonist. Our data further indicated that Con A administration increased the drug reduction index of TAM.

Overall, our findings suggested that Con A could be used as an adjuvant agent with TAM to improve its effectiveness as an anticancer agent.

Cancer is a progressive disease, its incidence and death rates are rapidly increasing globally. Numerous adverse effects are associated with the available interventions. Hence, the current study was undertaken to explore the anticancer effect of silver nanoparticles conjugated with berberine (AgNPs-BER) against Ehrlich solid carcinoma (ESC) in mice.

Male Swiss albino mice were allocated randomly into ESC, ESC+cisplatin (CP; 5 mg/kg), ESC+AgNPs-BER (20 mg/kg), and ESC+cisplatin and AgNPs-BER groups.

AgNPs-BER administration increased significantly the survival rate and decreased body weight and tumor size as compared to ESC group. Additionally, AgNPs-BER enhanced the development of oxidative stress in the tumor tissue as indicated by the increased lipid peroxidation (LPO) and nitric oxide (NO) accompanied by a decrease in the examined antioxidant proteins (glutathione (GSH) and its derived enzymes along with superoxide dismutase and catalase). AgNPs-BER was found also to trigger apoptotic cascade in the tumor cells through upregulating the mRNA expression of the pro-apoptotic proteins (Bax and caspase-3) and downregulating the mRNA expression of the anti-apoptotic protein (Bcl-2). Moreover, AgNPs-BER improved partially the histopathological alterations in the developed tumor tissue as compared to ESC group.

Collectively, AgNPs-BER could be applied as an antitumor agent due to its pro-oxidant, pro-apoptotic, and antiangiogenic effects.

About 55% of extremely-low-birth-weight (birth weight < 1000 g) and 23% of very low-birth-weight infants (birth weight < 1500 g) suffer from metabolic bone disease (MBD). There are limited data on the use of calcitriol (1, 25-dihydroxycholecalciferol) to prevent or treat MBD in preterm infants. Therefore, this study aimed to compare the preventive effect of calcitriol and cholecalciferol on the biochemical markers of MBD in preterm infants.

This study was a pilot randomized controlled trial conducted in the Alzahra teaching hospital of Tabriz University of Medical Sciences. we randomized 72 very-low-birth-weight infants in two groups of calcitriol 0.25 μg/day and cholecalciferol 400 IU/day. Biochemical markers, including serum 25-hydroxyvitamin D, alkaline phosphatase (ALP), phosphorus (P),calcium (Ca), parathyroid hormone (PTH), and tubular reabsorption of phosphate (TRP) levels were checked at baseline, three, and five weeks after medication, consecutively.

After three weeks of supplementation, infants in the cholecalciferol group had higher levels of serum 25-hydroxyvitamin D (P=0.001) and lower levels of urine phosphate (P=0.009); There were no significant differences in other biochemical markers. At the end of the fifth week, there was no significant difference between the two groups in terms of biochemical markers.

The study indicated that the use of cholecalciferol caused a lower urinary loss of phosphate in very-low birth-weight infants at a short time; however, these findings were not sustained during the study period.

Ondansetron hydrochloride (OND) is an antiemetic agent belongs to the 5-HT3 receptor antagonist class administrated widely in relieving nausea and vomiting which is the most common complication occurred after surgery. This study aimed to design and evaluate the physicochemical along with clinical effects of fast-dissolving nanofiber (FDN) of OND administrated sublingually to enhance the bioavailability, effectiveness, and patient compliance compared to orally disintegrating tablets (ODT).

Nanofibers were prepared by the electrospinning method, using polyvinyl alcohol and alpha-cyclodextrin as polymers and sodium saccharin as the sweetener. Physicochemical and mechanical characteristics of nanofibers were examined then the clinical evaluation was performed. Eighty patients volunteering for cataract surgery were randomly divided into two groups, one received FDN, and the other treated with ODT of OND after recovery and in case of relieving nausea. The severity of nausea was assessed using a visual analogue scale in the 6 and 24 h intervals after drug administration. The SPSS 25.0 statistical software and statistical tests were used to analyze the obtained data.

Nanofibers possessed a mean diameter of 159 ± 30 nm beside suitable physicochemical and mechanical characteristics. Statistical evaluations showed that both FDN and ODT formulations had an equal anti-emetic effect (P>0.05) on reducing the severity of nausea but the FDN formulation caused significantly higher levels of patients’ satisfaction (P<0.05) compared to the ODT.

Although both formulations had an almost equal anti-emetic effect, due to the benefits of this novel formulation including rapid disintegration, the ODT can be replaced by FDN.

Recently, nanoparticles were widely used in drug delivery. Fluconazole (FLZ) is a lipid-soluble antifungal, which is utilized in treating fungal infections. The current work aimed to investigate the characteristics and antifungal activity of FLZ nanosuspension.

FLZ nanosuspensions were prepared by ultrasonication (simple and containing polymer). Surfactants in various concentrations were dissolved in the deionized water, and the drug powder was dispersed in the surfactant solution by a high-speed homogenizer to achieve nanosuspension. The polymer was added to the selected formula. FLZ nanosuspension characteristics, including polydispersity, mean particle size, entrapment efficacy, and zeta potential, were assessed. The release profile via dialysis membrane, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (ATR-FTIR), and Transmission electron microscopy (TEM) were performed for nanosuspension evaluation. Antifungal activity against resistant strains of Candida albicans was defined according to the CLSI document guideline. To analyze the results, one-way ANOVA was used, followed by Tukey test.

The results showed that increased sonication time and hydrophilic-lipophilic balance (HLB) significantly affected particle size reduction. Moreover, modification in the formulation components had a significant effect on the drug release process, furthermore affecting the properties of the nanoparticles. ATR-FTIR showed no chemical interaction between FLZ and formulation components. Compare to FLZ, a significant reduction (p < 0.05) was detected in the MIC values of both FLZ-resistant and FLZ-susceptible strains of C. albicans against FLZ nanosuspension.

It can be concluded that the ratio and amount of surfactants, the HLB, and the sonication process have effects on the properties of the nanoparticle’s characteristics, and selected nanoparticles show suitable antifungal effect against resistant strains of C. albicans.

Flutamide is a non-steroidal anti-androgenic agent which is not only used in treating prostate cancer but also can be effective in some disorders such as androgenic alopecia and male pattern baldness. Several serious side effects for systemic administration of flutamide can be overcome by emulgel dosage form. Absorption enhancers can promote permeation of flutamide through skin. Percutaneous absorption of Flutamide emulgels with different concentrations of Transcutol P and Precirol ATO5 was studied.

Various emulgel formulations using different concentration of Transcutol P and Precirol ATO5 with 0.5 to 5 % w/w were prepared. Percutaneous absorption was tested with standard Franz Diffusion Cell equipment using full thickness rat skin. Drug concentrations in the samples were analyzed by High-Performance Liquid Chromatography (HPLC) equipped with UV-Vis detector at 305 nm.

The percutaneous absorption of flutamide emulgels formulated with enhancers was higher than control formulations. Enhancement ratio increased from 1.218 to 3.670 and 1.346 to3.900 for Precirol ATO5 and Transcutol P, respectively. Area under the Curve (AUC) increased by increase the enhancers’ concentration and a significant upsurge was seen in the concentration 1% for both enhancers.

The flutamide emulgel containing 1% Transcutol P showed more appropriate percutaneous absorption through the skin compared to others.

Meloxicam is a powerful analgesic and anti-inflammatory drug widely prescribed by physicians in current therapeutics. Because of the very low aqueous equilibrium solubility of meloxicam, this property has been studied in {2-propanol + water} mixtures from (293.15 to 313.15) K to expand the solubility database about pharmaceutical compounds in mixed solvents useful for homogeneous liquid dosage forms design.

Flask shaken method and UV-vis spectrophotometry were used for meloxicam solubility determinations. Jouyban-Acree model was challenged for solubility correlation. The van’t Hoff and Gibbs equations were employed here to calculate the respective apparent standard thermodynamic quantities for the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy. In addition, the inverse Kirkwood-Buff integrals were employed to compute the preferential solvation parameters of meloxicam by 2-propanol in the mixtures.

Meloxicam solubility increases with temperature arising and maximum solubilities are observed in the mixture of x1 = 0.70 at all temperatures. Jouyban-Acree model correlates the meloxicam solubility very well. Dissolution processes were endothermic in all cases and entropy-driven in the interval 0.20 ≤ x1 ≤ 1.00. Non-linear enthalpy–entropy relationship was observed in the plot of enthalpy vs. Gibbs energy exhibiting negative but variant slopes in the composition region 0.00 < x1 < 0.40 and variant negative and positive slopes in the other mixtures. Meloxicam is preferentially solvated by water in water-rich mixtures, it is apparently solvated by water in 2-propanol-rich mixtures, but it is preferentially solvated by 2-propanol in the composition interval of 0.19 < x1 < 0.78.

Solid-liquid equilibrium of meloxicam in {2-propanol + water} mixtures has been studied at several temperatures as a contribution to preformulation studies of homogeneous liquid pharmaceutical dosage forms based on this drug.

Phenolic compounds are one of the main groups of secondary metabolites responsible for multiple biological and pharmacological properties that play a vital role in improving human health quality. Encapsulation by spray dryer creates protection toward the phenolic compounds as an efficient way for increasing product performance.

The phenolic compounds of Satureja khuzistanica Jamzad (SKH) and S. rechingeri Jamzad (SRH) were enriched based on adsorbent resin column chromatography and the enrichment index was confirmed by HPLC-UV analysis. Gum Arabic, carboxylated chitosan, and pectin with the optimum percentage of 1% w/w used to encapsulate SKH and SRH by the spray drying technique.

Encapsulation yield was 38.18 – 59.00 %, particle size ranged 2.278 - 4.689 µm, and release time was between 4.08 - 82.08 min. The gum Arabic-based capsules showed the fastest and pectin-based revealed the slowest release time. The best statistical model explained a release mechanism was Korsmeyer model. Anomalous transport was observed from all formulas except SKH-gum Arabic (case-I transport), SKH-pectin, and SRH-carboxylated-chitosan (super case-II transport). The cytotoxic activity of encapsulate SKH’s revealed reducing the viability of AGS evaluated by the MTT compared with SRH’s.

Encapsulation by spray drying has proven to be a promising technique to improve the bioavailability, release time, and mechanism of functional polyphenolic compounds as medicines, food supplements, and food additives.

Pereskia aculeata and P. grandifolia are non-traditional Brazilian vegetables with high nutritional value used in traditional medicine. The antioxidant, anticholinesterase, molluscicidal, cytotoxic, and antiproliferative properties of hydroethanolic extracts of P. aculeata and P. grandifolia leaves (PAL, PGL) and fruits (PAF, PGF) are investigated in this study.

All extracts were prepared by maceration with ethanol 70%. Their antioxidant properties were assessed through DPPH, ABTS, FRAP, and β-carotene bleaching inhibition assays. A TLC bioautography method was employed to evaluate the inhibiting capacity of the acetylcholinesterase enzyme. The molluscicidal activity was tested against the snail Biomphalaria glabrata, which serves as an intermediate host for Schistosoma mansoni. The cytotoxic activity was assessed by an Artemia salina lethality test and the antiproliferative properties against seven human carcinoma cell lines.

Compounds with anticholinesterase activity were found in all extracts. Polar compounds present in PAF and PGL extracts were the most active (IC50 < 25 μg of dry mass) and had an adequate inhibition capacity of the AChE. PGF and PGL were classified as moderate (LC50 = 19.2 μg/ml) and modest molluscicidal agents (LC50 = 66.6 μg/ml), respectively. All extracts exhibited selective antiproliferative activity against human chronic myeloid leukemia cell lines (K562). PAL, PGL, and PGF presented potent antiproliferative activity (TGI ≤ 5 μg/ml).

Both species exhibited anticholinesterase, cytotoxic and antiproliferative properties. This research supports the potential of these species as sustainable sources of nutraceutical compounds.