Advanced Pharmaceutical Bulletin
Volume:12 Issue: 4, Sep 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative organism of COVID-19. Since this disease is considered new and does not have an approved curative protocol, many researchers have tackled the possible options for COVID-19 prevention and therapeutic approaches. We address herein the phenomena of cytokine storm (the main cause of death) associating with the late stage of COVID19. Cytokine storm is undertaken in an attempt to provide information about its possible underlying causes, and to clarify some points that can be of value in guiding treatment practices for a clinical trial.

Cancer is the leading challenge to human health since the dawn of early Egyptianmanuscripts, where they found tumour from fossils in the modernized 20th century. Increasingrate of incidence and death from cancer in the past few years is thought provoking. Among alltype of cancers, breast cancer is very common among women and diverse in character. Drugresistance is the challenging aspect for traditional chemotherapy.

Data was collected from online platform without any time restriction. After screeningand evaluation, 66 articles were considered for this study. This review is a summarized collectionof information from published studies on human genes associated with drug resistance in breastcancer treatment.

Analysis of these findings highlights the importance of MAP kinase and ABC genefamilies in creating resistance barriers. Genes involved in cell cycle alteration, apoptosis, andhippo pathway were also linked with drug resistance particularly in breast cancer.

The exact mechanism of chemotherapy resistance is still unresolved andunexplained the drug resistance seen in breast cancer patients were multifactorial. Druginduced up regulation or down regulation of genes contributes unusual protein expression andultimately leads to resistance. The ultimate focus of this review is to identify the genes havingpivotal role in chemotherapy resistance in breast cancer.

Unique mechanical properties, miscibility potency, and biodegradability are the threeprominent features of polycaprolactone (PCL), making it an attractive biomaterial whichcommonly applied in regenerative medicine and biomedical engineering. Different strategiesdeveloped for fabricating nanofibrous construct, electrospinning is a practical, simple, andefficient technique based on electro-hydrodynamic systems that use an electrified viscousfluid jet drawn by the air toward a collector at a changing electric potential. PCL electrospunbasednanofibrous composites as proper scaffolds are employed in stem cell-related research,particularly in tissue engineering, wound dressing, and systems designed for sending drugs.A compilation of mechanochemical properties and most common biological performance onPCL-based electrospun fibrous structures in biomedical application are included in this study.Therefore, electrospun PCL nanofiber applying has been presented, and after that, currentprogress and prospects have been discussed. Literature reviews revealed that electrospun PCLnanofibrous composites had gained significant attention in regenerative medicine, and thesestructures have shown notable development in mechanobiological properties. This evidence isa crucial success for biomedical strategies, especially in regenerative medicine.

Nano-theranostics (NTs) are versatile nanomaterials, explored in the current scenario of cancer therapy. A nano-theranostic material alone can diagnose and generate a therapeutic effect. Various materials have been explored for their NT action like gold and carbon-based material. The photon-based cancer theranostics has grabbed the attention of researchers due to their localized and trigger activated effect. NTs have shown a promising result in pre-clinical and clinical studies. The current review illustrates the meticulous efforts conducted by researchers across the globe to innovate and explore the photon-based cancer NT platforms of gold and carbon with their application in cancer therapy.

Cardiovascular disease (CVD) is a major concern for health with high mortality rates around the world. CVD is often associated with partial or full occlusion of the blood vessel network. Changes in lifestyle can be useful for management early-stage disease but in the advanced stage, surgical interventions or pharmacological are needed to increase the blood flow through the affected tissue or to reduce the energy requirements. Regeneration medicine is a new science that has provided many different options for treating various diseases, especially in CVD over the years. Stem cell therapy, gene therapy, and tissue engineering are some of the powerful branches of the field that have given patients great hope in improving their condition. In this review, we attempted to examine the beneficial effects, challenges, and contradictory effects of angiogenesis in vivo, and in vitro models’ studies of CVD. We hope that this information will be able to help other researchers to design new effective structures and open new avenues for the treatment of CVD with the help of angiogenesis and regeneration medicine in the future.

Microfluidics (MF) is the science dealing with the behavior, precise control, and manipulation of fluids as well as particles on the scale of tens to hundreds of micrometers. It is also utilized for chemical and biological applications, usually called micro–total analysis systems (µTAS) or lab-on-a-chip (LOC). MF is a fascinating and capable technology with various superior benefits compared to conventional macro-scale platforms, such as the lesser requirement of sample and reagent volumes, higher sensitivity, low cost, portability, faster processing of samples and potential to be automated and highly integrated to reduce human errors. The concept of transformation of meso to nanoliters using MF technology has shown its potential in the healthcare system for early diagnosis, and personalized medicine. The integrated multifunctional system with parallelization provides a better and faster process control. Minimization of the consumption of fluid makes the technology safer in every aspect of the development process, analysis, and storage. The impressive improvement in patient care and monitoring has led to the commercial motivation of the pharmaceutical industry to develop new drugs and modify existing products with better efficacy and safety in a cost-effective manner using MF technologies. Hence, the present review briefs on the applications of MF technology in the key issues of the drug discovery process, overcoming the limitations of development of analytical procedures and prosperous pharmaceutical manufacturing for novel controlled and targeted release dosage forms to fabricate quality products.

The concept of immunomodulation was proposed by Edward Jenner, while working on polio vaccine in 1796. Many of the autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, psoriatic arthritis and system lupus erythematosus, viral diseases and, some cancers are characterized with elevated levels of “immunocytokine” gene expression, including, tumor necrosis factor-α, various interleukins, cytotoxic T-cell antigen-4, B-cell activating factor. For the treatment of these diseases, the immunologically-based therapies play the major role. In these lines, the usage of phytomedicines as immunostimulants/ immunosuppressants have been enhanced considerably in last few decades and also used as a prophylactic treatment for various ailments. Phytochemicals such as flavonoids, terpenoids, polysaccharides, lactones, alkaloids, glycosides and saponins present in several plants, have been confirmed to exhibit immunomodulating properties. This review focuses on the traditional plants and their constituents which have been extensively used as immunomodulators. We have also highlighted the mechanism of action of these plant constituents related to autophagy and adjuvanticity of drugs.

Microparticulate drug delivery system (MDDS) has attained much consideration in the modernera due to its effectiveness in overcoming traditional treatment problems. Microparticles (MPs)are spherical particles of a diameter ranging from 10 μm to 1000 μm. MPs can encapsulateboth water-soluble and insoluble compounds. MDDS proved their efficacy in improvingdrugs bioavailability, stability, targeting, and controlling their release patterns. MPs also offercomfort, easy administration, and improvement in patient compliance by reducing drugstoxicity and dosage frequency. This review elucidates the fabrication techniques, drug release,and therapeutic application of MDDS. Further details concerning the therapeutic applicationsof antidiabetic drugs-loaded MPs were also reviewed, including controlling drugs release bygastroretention, improving drugs dissolution, reducing side effects, localizing drugs to the site ofdisease, improving insulin stability, natural products loaded with MPs, sustained drug release,mucosal delivery, and administration routes. Additionally, the current situation and futureprospects in developing MPs loaded with antidiabetic drugs were discussed.

Cancer is a serious debilitating disease and one of the most common causes of death. In recentdecades the high risk of various cancers enforced scientists to discover novel prevention andtreatment methods to diminish the mortality of this terrifying disease. Accordingly, its preventioncan be possible in near future. Based on epidemiological evidence, there is a clear link betweenpathogenic fungal infections and cancer development. This association is often seen in peoplewith weakened immune systems such as the elderly and people with acquired immunodeficiency(AIDS). Carcinoma in these people is first seen chronically and then acutely. Although thedifferent genetic and environmental risk factors are involved in carcinogenesis, one of the mostimportant risk factors is fungal species and infections associating with cancers etiology. Now itis known that microbial infection is responsible for initiating 2.2 million new cancer cases. Inthis way, many recent studies have focused on investigating the role and mechanism of fungalinfections in diverse cancers occurrence. This review provides a comprehensive frameworkof the latest clinical findings and the association of fungal infections with versatile cancersincluding esophageal, gastric, colorectal, lung, cervical, skin, and ovarian cancer.

During the last few decades, nanotechnology has gained many applications in almost all fieldsof life because of the unique properties of nanoparticles (NPs). Nanotechnology has speciallymarked its name in the field of medicine. However, NPs toxicity is detrimental to human healthand is a prime concern in applied medicine. They can cause insomnia, vertigo, madarosis,epistaxis, hypokalemia, lymphopenia, Alzheimer’s and Parkinson’s diseases, etc. There is agap in knowledge regarding the study of the toxicological effects of NPs. Mechanisms thatare responsible for this toxicity are not fully understood yet. Phytochemicals have naturaltherapeutic effects of reducing metal NPs’ toxicity by acting as stabilizers and nontoxicreducing agents. However, the interaction between phytochemicals and NPs is remained to beelucidated. This review will provide in-depth knowledge about the various types of inorganicNPs and their associated toxicities, key parameters determining the toxic behaviour of NPs, andthe mechanisms behind their cytotoxicity. It also emphasizes the need for further research tounderstand the interaction between various phytochemicals and NPs for therapeutic purposes.

Neurological disorders such as Alzheimer’s disease, Parkinson’s disease, dementia, epilepsy,depression, migraine etc. are affecting more and more elderly people’s day by day. Conventionalroute of administration to treat these diseases has to face a major hindrance that is bloodbrain and blood-cerebrospinal fluid (CSF) barrier to achieve desired concentration of drug atthe site of action for therapeutic effect. Hence, intranasal route of delivery is considered aspromising and alternative route to achieve desired goals. In last four decades, brain targetingstrategies are widely studied and considered having great potential by researchers; especiallyintranasal delivery owing to its benefits. Various nano formulations such as nanoemulsions,nanosuspensions, hydrogels, in situ gels, dendrimers and lipidic formulations are studiedwidely. Lipid nano formulations especially second generation nanostructured lipid carriersoffer greater advantages in terms of stability, fabrication techniques, scalability, drug loadingand drug targeting. Nanostructured lipid carrier (NLCs) constitute of two major componentsviz solid lipid and liquid lipid in a specific ratio. In this review, authors have discussed aboutthe possible synergistic actions of oils/liquid lipids with synthetic drugs resulting into greattherapeutic benefits.

Radiotherapy is one of the most important therapeutic options used to treat cancers.Radiation effects can be improved using nanoparticles and chemotherapeutic drugs asradiosensitizing agents. The aim of the present study was to evaluate the effects of folic acidconjugatedgold nanoparticles (GNP-F) in combination with doxorubicin (DOX) and x-Rayirradiation in colorectal cancer (CRC) cell line (HT-29).

The cell viability assay (WST-1) was performed to study the cytotoxic effects ofdifferent concentrations of DOX and GNP-F after 24 and 48 hours treatments. Then, the effectsof the GNP-F, X-Ray irradiation, and DOX drug in single and combined treatments wereexamined after 24 and 48 hours treatment with effective doses. Likewise, the caspase 3 geneexpression ratio and the caspase 3 activity were assessed after 48 h treatment. Moreover, themalondialdehyde (MDA) level was determined in treated and untreated cells.

When GNP-F (at a concentration of 70 μM) was combined with X-ray irradiation (2Gy) and DOX drug, induced more cytotoxic effects compared to the control group. The resultsof cell viability assay showed that GNP-F + X-Ray in combination with a low concentrationof DOX (0.25 × IC50) enhanced the cytotoxic effects of cells compared to related singletreatments. Caspase 3 gene expression ratio and caspase 3 activity increased in double andtriple combination treatments in comparison with the single groups. Moreover, the MDA levelincreased in triple combination compared to the single treatments.

Our findings confirmed the potential anti-cancer effects of the GNP-F and DOX incombination with X-Ray irradiation in CRC cells.

Diabetic somatic neuropathy is one of the most prevalent complications in type 1diabetes mellitus (T1D). Many treatments were investigated to alleviate the pain associatedwith this condition. Capsaicin is a naturally occurring lipophilic alkaloid that proved to be aneffective and safe treatment of chronic painful disorders. Despite the known therapeutic benefitsof capsaicin, the conventional topical formulations have limited bioavailability. Therefore, thecurrent study aims to develop capsaicin nanoemulgel to increase skin permeation and enhanceits activity against neuropathic pain.

Low-energy emulsification method was used to prepare nanoemulsions, usingeucalyptus oil as the oily phase, Tween 80 as a surfactant, propylene glycol, ethanol andisopropyl alcohol as co-surfactants. Pseudo-ternary phase diagrams were constructed toinvestigate and optimize the formulation. Subsequently, the optimum formulation wasformulated as a nanoemulgel and investigated for, skin permeation using Franz diffusion cell,and diabetic neuropathy (DN) management using alloxan-induced diabetic mice.

The selected nanoemulsion containing 0.05% capsaicin is composed of 8 % oil,24 % Smix (Tween 80: isopropyl alcohol 2:1 w/w) and 68 % water. It is characterized bynanosized globules (28.15 ± 0.24 nm) with a relatively low polydispersity index (0.27 ± 0.05).The nanoemulgel revealed circa 4-fold increase in capsaicin cumulative permeation whencompared to the conventional gel, and an improvement in its antinociceptive properties wasobserved in the treated diabetic mice (P < 0.05).

The selected capsaicin nanoemulgel would be a promising transdermal formulationthat may alleviate diabetic neuropathy in T1D patients.

Felodipine, is a calcium-channel antagonist used for hypertension and anginapectoris. It is practically insoluble in aqueous media and shows low oral bioavailability (15%-20%). This investigation aims to prepare and characterize oral felodipine lipid-polymer hybridnanocarriers (LPHNs) to increase solubility and control delivery for increasing bioavailabilityand enhance patient compliance.

The newly microwave-based method was prepared with felodipine LPHNs (H1-H35)successfully. The (H1-H35) were subjected to thermodynamic stability experiments. After that,select nine felodipine LPHNs (F1-F9) that have smart physical stability for further optimizationof different characterization processes.

The felodipine LPHNs (F4) are considered the most optimized formula. It wascharacterized by lower particle size (33.3 nm), lower PDI (0.314), high zeta potential (13.6mV), entrapment efficiency is (81.645% w/w), drug loading is (16.329% w/w), the pH value is4, excellent percent of light transmittance (95.5%), pseudoplastic rheogram, significantly high(P < 0.05) dissolution rate with sustained drug delivery and success ex-vivo intestinal permeationattributes. The (F4) subject for further investigations of Fourier transformed infrared spectroscopy(FTIR), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The resultsof FTIR, AFM, and TEM indicate there is no interaction between the felodipine and excipientsand that the particulate system in the nanoscale dispersion system confirms the high stability.

The optimized felodipine LPHNs (F1-F9) formulations were smart formulations forsustained oral delivery of felodipine and that F4 was the most optimized formula according toits characterization processes.

To investigate the in vitro anti-skin-aging properties of Cratoxylum formosumextract and encapsulate this plant extract in nanostructured lipid carriers (CFE-NLCs) fordermal application.

The biological properties of the plant extract, including enhanced procollagen typeI synthesis and anti-matrix metalloproteinase activity, were evaluated to assess its cosmeticbenefits. An artificial neural network (ANN) coupled with K-fold cross-validation was appliedto investigate the effects of the formulants and optimize the CFE-NLCs. The physicochemicalproperties, percutaneous absorption, and irritation potential of the CFE-NLCs were analyzed.

Liquid chromatography-mass spectrometry analysis revealed that CFE contained5-O-caffeoylquinic acid as the vital constituent. Appropriate skin-care properties were alsodemonstrated with respect to enhanced type I procollagen synthesis and the inhibition of MMP-1, MMP-3, and MMP-9 in primary human dermal fibroblasts. The optimal CFE-NLCs exhibitedbetter skin absorption and biocompatibility and lower irritation potential than the free botanicalextract solution.

The findings obtained highlight CFE-NLCs as promising skin-care ingredients.

Today, the discovery of novel and effective chemotherapeutic compounds is the mainchallenge in cancer therapy. In recent years, the anti-tumoral activity of natural naphthoquinonejuglone (JUG), present in different parts of walnut trees, has received considerable interest. Thepurpose of the current study was to prepare and evaluate the in vitro antiproliferative activity ofJUG-loaded bovine serum albumin nanoparticles (JUG-BSA NPs).

BSA NPs and JUG-BSA NPs were prepared using the desolvation technique. The NPswere characterized for their particle size (PS), zeta potential (ZP), drug loading (DL) capacityand encapsulation efficiency (EE). The anti-proliferative activity of JUG-BSA NPs was evaluatedon A431 and HT29 cancer cell lines using cellular uptake and MTT assays.

The PS and ZP values of JUG-BSA NPs were 85 ± 6.55 nm and −29.6 mV, respectively.The DL capacity and EE were 3.7% to 5% and 50.4% to 94.6%, respectively. The cytotoxicityof JUG-BSA NPs was significantly less on both cultured A431 and HT29 cells at the studiedconcentrations when compared to free JUG. However, the effect was not very substantial,particularly at high levels.

In conclusion, BSA NPs can be used as a suitable and safe carrier for the deliveryof JUG, a cytotoxic hydrophobic natural compound.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer. The maincause of death in ESCC is related to relapse, metastasis, and resistance to cancer therapy. Recentstudies have shown that a minor subset of cancer cells, known as cancer stem cells (CSCs), areresponsible for tumor formation initiation and cancer progression. Understanding the genesassociated with CSCs and metastasis can help in targeted cancer therapy. The aim of this studywas to assess the expression of LAMB3 and TOP2A metastasis-associated genes in CSCs andadherent cells in the xenograft mouse model.

Esophageal CSCs were enriched by the sphere formation method. The expressionlevel of LAMB3 and TOP2A genes were evaluated in spheres and adherent cells in vitro byqRT-PCR. A xenograft mouse model was established to investigate the tumorigenesis andmetastasis potential by subcutaneous and tail vein injection of CSCs and adherent YM-1 cells.Consequently, LAMB3 and TOP2A expression at the mRNA level was assessed in tumors.Immunohistochemistry was also used to evaluate the LAMB3 expression at the protein levelin tumors.

CSCs-derived tumor was developed more quickly than the adherent cells-derivedtumor. LAMB3 at mRNA and protein level was significantly down-regulated in sphere-derivedtumor compared with adherent cells-derived tumor (P value <0.05). TOP2A expression wasalmost similar in both sphere cells and adherent cells and there was no significant difference.

we concluded that YM-1 spheres have CSCs characteristics in vitro with highcapability of tumorigenicity in vivo. Our results were also shown that the LAMB3 expressionwas decreased in YM-1 spheres suggesting LAMB3 association with sphere formation.

Colorectal cancer is one of the most prevalent cancers, worldwide. The presentstudy aimed to examine the effects of Scrophularia oxysepala (SO) methanolic extract on1,2-dimethylhydrazine (DMH) induced colon cancer model in the Wistar rats.

The animals administered DMH (40 mg/kg/S.C.) biweekly for 2 weeks to induceaberrant crypt foci (ACF). Other groups of animals were given the SO extract (50, 100 and200 mg/kg/orally once/day) either before or after the DMH treatments. In the end, all animalswere killed and at necropsy, the colon samples examined. The ACF, aberrant crypt (AC), cryptmultiplicity (CM), caspase 3 protein and apoptosis measurement were performed.

The SO extract significantly (P<0.001) decreased the number of AC, ACF, and CM inall pre- and post-treated groups and caused significant increases in caspase 3 and apoptosisas compared to the DMH group. However, post-treated animals showed significantly moreeffective than pre-treatment groups. Methanolic extract of SO showed a chemopreventivepotential, by effectively reducing the number of AC, ACF, and CM and increasing caspase 3protein and apoptosis.

One of the possible mechanisms might be involved in the induction of apoptosisthrough the caspase 3 mediated pathway.

Breast cancer is one of the most commonly diagnosed types of cancer worldwide. Thiscancer is treated with various methods like mastectomy, chemotherapy, hormone therapy, andradiotherapy. Among them, targeted therapy, like microRNA (miRNA) replacement therapy, isconsidered a new approach to treating breast cancer.

Data analysis from TCGA datasets were used to investigate the expression of hsamiR-146a-5p in breast cancer. MTT assay was used to evaluate the viability of MDA-MB-231cells after hsa-miR-146a-5p ectopic expression. A wound-healing assay was used to observemigration in the MDA-MB-231 cell line and the effect of the hsa-miR-146a-5p ectopic expressionon migration. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR)was used as a method to determine the effect of the hsa-miR-146a-5p ectopic expression onthe expression of CXCR4, β-catenin, MMP2, MMP9, and Vimentin genes known to be involvedin invasion and migration of MDA-MB-231 cells.

Our results indicated that hsa-miR-146a-5p is not involved in apoptosis in the MDAMB-231 cells, while it is highly effective in migration inhibition. MMP9, MMP2, CXCR4, andVimentin expressions were suppressed by hsa-miR-146a-5p induction; however, it induced theexpression of β-catenin.

Some non-coding RNAs, such as hsa-miR-146a-5p, are effective in breast cancertargeted therapy. As cancer is a complicated disorder, therefore the combination of therapiesmight lead to novel therapeutic strategies.

Autism is a multifactorial neurodevelopment disease and it has not been disclosed asa hypoglutamatergic or hyperglutamathergic disease. Ceftriaxone is an antibiotic that increasesglutamate transporter-1 (GLT-1) expression in the brain in chronic use. In our study we aimed toinvestigate the effects of different doses of ceftriaxone in postnatal period in male mice exposedto valproic acid (VPA) at 12.5th day of pregnancy.

A total of 96 BALB/c male mice were divided into 12 groups (n = 8 animals pergroup). Ceftriaxone (50, 100, 200 mg/kg/d) or saline was given to the male offsprings born frompregnant mice administered VPA and/or saline, between days 47 and 55. Dihydrokainic acid(10 mg/kg), a GLT-1 inhibitor, was administered intraperitoneally to evaluate whether GLT-1mediates the effect of ceftriaxone. Three chamber sociability and social interaction test and therota rod test were performed in all groups on days 54 and 55. GLT-1 levels in the hippocampuswere measured by immunohistochemistry (IHC) and western blotting (WB).

In our study, autism-like behaviors were observed in male offsprings that were exposedto VPA in the intrauterine period. Chronic ceftriaxone administration has no curative effect onbehavioral impairment seen in autism.

Our results show that ceftriaxone did not exert significant therapeutic effect onVPA-induced mouse model of autism.

Breast cancer has become as a serious public health concern worldwide. Breastcancer cells release exosomes into the circulatory system, which are easily accessible for furtheranalysis like cancer diagnosis. In this study, we aimed to investigate expression of circulatingexosomal miRNAs (miRs) in the serum of individuals with breast cancer and healthy controls.

Exosomes were collected from serum samples using a commercial kit and characterizedby scanning electron microscopy (SEM) and flow cytometry analysis. Expression of miRs suchas miR-21, miR-155, miR-182, miR-373, and miR-126 were evaluated by real-time PCR.

The result showed that the expression level of exosomal miR-21, miR-155, miR-182, and miR-373 in the serum of breast cancer patients was higher than of those controls(P<0.05). However, expression of miR-126 did not change between breast cancer and controlindividuals (P > 0.05).

Our results showed a different miRs expression pattern between breast cancer andhealthy samples, supposing potential biomarkers for breast cancer. Further studies focusing onthese miRs are required to confirm our findings.