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Abstract: A unique kind of pluripotent cell, i.e., Induced pluripotent stem cells (iPSCs), now being targeted for iPSC synthesis, are produced by reprogramming animal and human differentiated cells (with no change in genetic makeup for the sake of high efficacy iPSCs formation). The conversion of specific cells to iPSCs has revolutionized stem cell research by making pluripotent cells more controllable for regenerative therapy. For the past 15 years, somatic cell reprogramming to pluripotency with force expression of specified factors has been a fascinating field of biomedical study. For that technological primary viewpoint reprogramming method, a cocktail of four transcription factors (TF) has required: Kruppel-like factor 4 (KLF4), four-octamer binding protein 34 (OCT3/4), MYC and SOX2 (together referred to as OSKM) and host cells. IPS cells have great potential for future tissue replacement treatments because of their ability to self-renew and specialize in all adult cell types, although factor-mediated reprogramming mechanisms are still poorly understood medically. This technique has dramatically improved performance and efficiency, making it more useful in drug discovery, disease remodeling, and regenerative medicine. Moreover, in these four TF cocktails, more than 30 reprogramming combinations were proposed, but for reprogramming effectiveness, only a few numbers have been demonstrated for the somatic cells of humans and mice. Stoichiometry, a combination of reprogramming agents and chromatin remodeling compounds, impacts kinetics, quality, and efficiency in stem cell research.

Store-operated Ca2+ entry (SOCE) machinery, including Orai channels, TRPCs, and STIM1, is key to cellular calcium homeostasis. The following characteristics of mitochondria are involved in the physiological and pathological regulation of cells: mitochondria mediate calcium uptake through calcium uniporters; mitochondria are regulated by mitochondrial dynamic related proteins (OPA1, MFN1/2, and DRP1) and form mitochondrial networks through continuous fission and fusion; mitochondria supply NADH to the electron transport chain through the Krebs cycle to produce ATP; under stress, mitochondria will produce excessive reactive oxygen species to regulate mitochondria-endoplasmic reticulum interactions and the related signalling pathways. Both SOCE and mitochondria play critical roles in mediating cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia-reperfusion injury. All the mitochondrial characteristics mentioned above are determinants of SOCE activity, and vice versa. Ca2+ signalling dictates the reciprocal regulation between mitochondria and SOCE under the specific pathological conditions of cardiomyocytes. The coupling of mitochondria and SOCE is essential for various pathophysiological processes in the heart. Herein, we review the research focussing on the reciprocal regulation between mitochondria and SOCE and provide potential interplay patterns in cardiac diseases.

Mesoporous bioactive glass demonstrated valuable biomedical applications especially in the field of bone regeneration and drug delivery. For the treatment of cancer by chemotherapy, controlled drug delivery system is one of the significant methods. In this work, silver oxide doped mesoporous bioactive glass nanoparticles (Ag2O-MBG NPs) were developed for the controlled release of doxorubicin as a model drug. Ag2O-MBG NPs were prepared by using the sol-gel method and employing pluronic 123 as an internal template. The prepared Ag2O-MBG NPs were characterized by energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for composition, shape, morphology, and size. Surface area and pore size were determined by the Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) method respectively. When immersed in simulated body fluid (SBF), hydroxycarbonate apatite (HCAp) formation was demonstrated as established by Fourier Transform Infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The as-synthesized Ag2O-MBG NPs did not show any detrimental effects during MTT assay and in vivo tissue histopathology. Doxorubicin (DOX) was encapsulated with an efficiency of 84% and its release was observed to be affected by the drug loading concentration (0.2–1.0 mg/mL) and pH (6.4–8.4) of the release media. DOX release was of 93% was witnessed approximately for two weeks at a slight acidic pH of 6.4. At 11.88 μg/mL of DOX-Ag2O-MBG NPs, notable inhibitory effects on the viability of the MG-63 osteosarcoma cancer cells were observed. These features proved that the Ag2O-MBG NPs system is effective for bone tissue regeneration and bone cancer treatment.

Store‐operated Ca2+ entry (SOCE) machinery, including Orai channels, TRPCs, and STIM1, is key to cellular calcium homeostasis. The following characteristics of mitochondria are involved in the physiological and pathological regulation of cells: mitochondria mediate calcium uptake through calcium uniporters; mitochondria are regulated by mitochondrial dynamic related proteins (OPA1, MFN1/2, and DRP1) and form mitochondrial networks through continuous fission and fusion; mitochondria supply NADH to the electron transport chain through the Krebs cycle to produce ATP; under stress, mitochondria will produce excessive reactive oxygen species to regulate mitochondria‐endoplasmic reticulum interactions and the related signalling pathways. Both SOCE and mitochondria play critical roles in mediating cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia‐reperfusion injury. All the mitochondrial characteristics mentioned above are determinants of SOCE activity, and vice versa. Ca2+ signalling dictates the reciprocal regulation between mitochondria and SOCE under the specific pathological conditions of cardiomyocytes. The coupling of mitochondria and SOCE is essential for various pathophysiological processes in the heart. Herein, we review the research focussing on the reciprocal regulation between mitochondria and SOCE and provide potential interplay patterns in cardiac diseases.

Polymer blending is a promising method to overcome stability obstacles induced by physical aging and swelling of implant scaffolds prepared from amorphous polymers in biomedical application, since it will not bring potential toxicity compared with chemical modification. However, the mechanism of polymer blending still remains unclearly explained in existing studies that fail to provide theoretical references in material R&D processes for stability improvement of the scaffold during ethylene oxide (EtO) sterilization, long-term storage, and clinical application. In this study, amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PELA) was blended with amorphous poly(lactic-co-glycolic acid) (PLGA) because of its good miscibility so as to adjust the glass transition temperature (Tg) and hydrophilicity of electrospun PLGA membranes. By characterizing the morphological stability and mechanical performance, the chain movement and the glass transition behavior of the polymer during the physical aging and swelling process were studied. This study revealed the modification mechanism of polymer blending at the molecular chain level, which will contribute to stability improvement and performance adjustment of implant scaffolds in biomedical application.

In this study, biocompatible and biodegradable polyurethanes (PUs) were prepared by using different amino acids as chain extenders. Their structure and morphology were determined by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis whereas their mechanical properties were evaluated by universal testing machine. These PUs were not only screened for their in vitro and in vivo cytotoxicity but also evaluated for their water uptake, swelling behavior, hydrolytic degradation and employed as pH-responsive drug delivery carriers. An anti-cancer drug imatinib was loaded to these PUs with 94% of loading efficiency and its release behavior was studied at different pH values. All the PUs showed a persistent local release for >300 h. The results exhibited that drug released at physiological pH (7.4) is far lesser as compared to the acidic and basic pH of the release media. At acidic pH, 82% of the drug has been released as compared to the 41% at physiological pH. The results clearly demonstrate that these PUs are safe and can be used as intelligent drug release matrices for targeted drug delivery.

Waterborne biodegradable polyurethane–urea (WPUU) elastomer is a revolutionary step in the field of green polymer chemistry. In the present study, emulsifier–free biodegradable WPUU elastomer was synthesized by using lysine as an internal emulsifier as well as a chain extender. WPUU elastomer was used as the stimuli–responsive drug release matrix, loaded by cisplatin as a model anticancer drug. Sustained drug release was studied by changing pH (4.4–7.4), drug release medium, and NCO/OH ratio (3–4). Furthermore, significantly inhibitory effect against Sw–620 cancer lines was observed. Highest cumulative drug release of 71.9% was observed at pH of 7.4 in phosphate buffer saline (PBS) by the system having NCO/OH = 3 for 250 h. The oxidative degradation was evaluated in CoCl2/H2O2 solution. Mechanical properties were tested by using the mechanical testing machine. The synthesized WPUU films exhibited high thermal stability, hardness, tensile strength and hydrophobicity.

A novel diamine 4-(4-aminophenoxy)butyl-4-aminophenyl ether (ABAE) was synthesized as a chain extender (CE) by a quick and facile method using microwave reactor. CE was used for the preparation of stimuli-responsive Polyurethane-urea elastomer (PUU) with the ratio of NCO/OH from 2 to 2.5. Synthesized PUU was characterized with the help of Fourier transform infrared spectroscopy (FTIR), derivative thermogravimetric analysis (DTG), and scanning electron microscopy SEM. PUU films were loaded with an anti-cancer drug “doxorubicin”. Drug release kinetics were studied in different solvents, at different pH values and with different NCO contents of PUU. The maximum of 45% cumulative drug release was observed in DMSO while the drug release increased with the decrease in pH and a maximum cumulative release of 47% was observed at acidic pH of 4.4. The minimum drug was released from the one, which was crosslinked with highest ratio (2.5) of NCO/OH. So, we can say that drug release can easily be adjusted under different conditions and environments with the help of these stimuli-responsive media.

A bifunctional mesoporous bioactive glass (MBG) with composition (49SiO2·20CaO·20Na2O·7K2O·4P2O5 mol%) was synthesized by a facile sol-gel method, using polyethylene glycol (PEG 6000) as a soft template. The structure, morphology (spherical with approximate size 1μm) and composition of MBG were determined by fourier transform infrared spectroscopy, the scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX), respectively. The surface area (189.53m2g-1 with the pore size of 21nm) of MBG was measured by Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) analysis. The formation of hydroxyapatite (HAp) layer on the glass surface upon immersion in simulated body fluid (SBF) was monitored through X-ray diffraction (XRD) which indicates enhanced bioactivity as compared to previous studies. The animals study, protein adsorption ability, and cytotoxicity investigations show no tissue damage, good biomedical properties and no encumbrance with cell cycle (even at a concentration of 80μg/mL). Moreover, the cell proliferation analysis reveals the non-toxic property of MBG at a concentration of 20μg/mL. Notably, a cumulative drug (ciprofloxacin, an antibiotic) release of 75% was observed for first 48h and the further release of 90% was observed over a period of two weeks. The synthesized MBG also shows osteoblast activity and bone mineralization as revealed by alkaline phosphatase activity (ALP) and osteocalcin formation.

In this work, ultrapure hexagonal BaFe12O19 nanoferrite was synthesized by a facile co-precipitation method. Formation of single phase was analyzed by using wide angle X-ray diffraction. Crystallite size was found to increase from 50 nm to 78 nm when annealing temperature increased from 800 °C to 1000 °C, respectively. Ferrimagnetic behavior with moderate value of saturation magnetization and coercivity were studied at room temperature with the help of vibrating sample magnetometer (VSM). The electromagnetic radiation (EMR) absorption properties were studied in the frequency range of 2–18 GHz by using Vector Network analyzer (VNA). The maximum EMR absorption of −26.52 dB was observed at a frequency of 5.79 GHz. The FTIR spectra confirm tetrahedral and octahedral sites in BaFe12O19 structure. The surface morphology was analyzed by scanning electron microscopy (SEM), which reveals that the particles are agglomerated into irregular shapes. Particle size was measured with transmission electron microscopy (TEM), which was in correlation with the already calculated size from x-ray diffraction (XRD) spectra.

The main aim of this research was to study the effects of size and concentration of the hard segments on thermal stability, solvent resistance, hardness and drug delivery applications in polyurethane-urea (PUU) elastomers. Four diamines having different aliphatic chains, were synthesized and used as chain extenders (CE) to synthesize PUU. NCO/OH ratio was changed from 2-2.5 to study the effect of concentration of hard segments. Structure, morphology, thermal stability, hardness, solvent resistance, drug delivery and mechanical properties of polyurethane-urea elastomers were examined by means of fourier transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WAXD), thermogravimetric analysis (TGA), shore durometer, UV/Vis spectrophotometer and universal testing machine (UTM) respectively.

Correction for ‘Magnetic mesoporous bioactive glass for synergetic use in bone regeneration, hyperthermia treatment, and controlled drug delivery’ by Muhammad Saif Ur Rahman et al., RSC Adv., 2020, 10, 21413–21419, DOI: 10.1039/C9RA09349D.

An upregulated expression of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in hepatocellular carcinomas (HCC) associates with poor prognosis, but the underlying mechanism for expression regulation has not been elucidated. HAI-1 was expressed in HCC cell line Hep3B cells at a high level but absent or has a low level in other HCC cell lines HepG2 and SMMC7721 and immortal normal liver cell line L02 at transcriptional and translational levels, respectively. A dual-luciferase reporter assay showed that transcriptional activity of HAI-1 in the promoter region (-452 bp to -280 bp from the mRNA start site) was strongly enhanced in Hep3B and SMMC7721. Bisulfite genomic sequencing results of the HAI-1 promoter region showed an inverse correlation between levels of promoter methylation and expression in HCC cells. The expression level of HAI-1 in SMMC7721, HepG2, and L02 cells was elevated after 5-Aza-2′-deoxycytidine treatment. Hypomethylation of the HAI-1 promoter region contributed to the elevated HAI-1 expression in HCC tissues. In addition, the hypomethylation of the HAI-1 promoter region correlated with poor differentiation status of HCC tissues. Our findings indicate that promoter hypomethylation is an important mechanism for aberrant HAI-1 expression regulation in HCC.

The materials capable of sustained drug release are highly desired in the biomedical field, and for this purpose, mesoporous bioactive glass (MBG) and polyurethanes (PUs) are being used along with various other materials. However, MBG is highly brittle and PUs suffer from the lower tensile strength value. Therefore, to overcome these shortcomings, bioactive nanocomposites were designed and fabricated by using MBG and biodegradable PUs. MBG with variable percentages was used as filler in arginine and starch-based PU matrices. The structural, mechanical and physicochemical properties were evaluated by fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), stress-strain curves and MTT assay. All the nanocomposites exhibited high cell viability (96–100%) and are therefore designated as biocompatible. The young's modulus is in the range of 0.5–0.8 MPa, which perfectly matches with that of cancellous bones. The nanocomposites were further studied for sustained drug delivery of an anti-cancer drug, imatinib. There was no burst effect and 52–84% of the drug was released over a period of three weeks. Consequently, these nanocomposites behaved as reservoirs for sustained drug release and can be applied for reducing the dose frequency where required.

Gastric cancer is one of the most common malignancies worldwide. Understanding the molecular nature of gastric cancer is essential for the development of effective and personalized therapies. Several molecular signal transduction pathways drive tumorgenesi...

Breast cancer is the main threat around the world. Estrogen and estrogen receptors (ER) assume a noteworthy part in breast disease movement and advancement. Breast cancer is the most pervasive disease in women, every year more than 200,000 new cases analyz...

Mitochondria are important for energy production and cardiomyocytes homeostasis. OMA1, a metalloendopeptidase, initiates the proteolytic process of pro-fusion protein, OPA1, to deteriorate mitochondrial structure and function. In this study, mouse embryonic fibroblasts (MEFs) and neonatal mouse cardiomyocytes (NMCMs) subjected to hypoxia-reperfusion (H/R) and/or H2O2 were used to mimic oxidative stress in the heart following ischemia-reperfusion (I/R). In vitro experiments demonstrated that H/R insult and H2O2 stimulation induced self-cleavage of OMA1 and subsequent conversion of OPA1 from long form to short form, leading to mitochondrial fragmentation, cytochrome c release, and apoptosis. By using Molecular Operating Environment (MOE) to simulate the binding interaction of 2295 phytochemicals against OMA1, epigallocatechin gallate (EGCG) and betanin were selected as candidates of OMA1 inhibitor. We found that EGCG directly interacted with OMA1 and potently inhibited self-cleavage of OMA1, leading to attenuated OPA1 cleavage. This study suggests that OMA1 inhibition induced by EGCG can serve as a potential approach to treat cardiac I/R injury.

Retinitis pigmentosa is a group of genetically transmitted disorders affecting 1 in 3000–8000 individual people worldwide ultimately affecting the quality of life. Retinitis pigmentosa is characterized as a heterogeneous genetic disorder which leads by progressive devolution of the retina leading to a progressive visual loss. It can occur in syndromic (with Usher syndrome and Bardet-Biedl syndrome) as well as non-syndromic nature. The mode of inheritance can be X-linked, autosomal dominant or autosomal recessive manner. To date 58 genes have been reported to associate with retinitis pigmentosa most of them are either expressed in photoreceptors or the retinal pigment epithelium. This review focuses on the disease mechanisms and genetics of retinitis pigmentosa. As retinitis pigmentosa is tremendously heterogeneous disorder expressing a multiplicity of mutations; different variations in the same gene might induce different disorders. In recent years, latest technologies including whole-exome sequencing contributing effectively to uncover the hidden genesis of retinitis pigmentosa by reporting new genetic mutations. In future, these advancements will help in better understanding the genotype–phenotype correlations of disease and likely to develop new therapies.

Correction for ‘Magnetic mesoporous bioactive glass for synergetic use in bone regeneration, hyperthermia treatment, and controlled drug delivery’ by Muhammad Saif Ur Rahman et al., RSC Adv., 2020, 10, 21413–21419, DOI: 10.1039/C9RA09349D.

For treating bone cancer, controlled drug delivery is an important strategy. Bioactive scaffolds are widely used biomaterials due to their usefulness in localized drug delivery. The aim of this study was to develop mesoporous bioglass (MBG) with improved bioactivity and controllable drug delivery rate. By using pluronic 123 (P123) as a template, a facile sol-gel route was employed for the synthesis of MBG nanoparticles (NPs). The composition of the prepared sample was estimated by using energy dispersive X-ray spectroscopy (EDX). These nanoparticles demonstrated the specific surface area of 310m2/g and pore size of 13nm as measured by brunauer-emmett-teller (BET) and barrett-joyner-halenda (BJH) method, respectively. The spherical shape of NPs was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Imatinib (IMT); an anti-cancer drug was loaded with the efficiency of 77.59%. The drug release kinetics were precisely controlled by changing the pH (4.4 to 10.4) as well as drug loading concentration (0.2-1.0mg/mL). The maximum cumulative drug release of 81% was observed over a time period of 250h at pH of 4.4. Importantly, significant inhibitory effects on the viability of the MG-63 osteocarcinoma cancer cells at 12.19μg/mL of IMT-MBG were observed. Furthermore, MBG demonstrated ionic dissolution with the release of Ca, K, Si, Na, and P ions upon immersion in simulated body fluid (SBF), which support the formation of hydroxycarbonate apatite (HCA), as confirmed by wide-angle X-ray diffraction (WAXD) pattern and fourier transform infrared (FTIR) spectroscopy. These features proved that IMT-MBG system is effective for bone tissue regeneration and bone cancer treatment.

Mitochondrial homeostasis is critical for keeping functional heart in response to metabolic or environmental stresses. Mitochondrial fission and fusion (mitochondrial dynamics) play essential roles in maintaining mitochondrial homeostasis, defects in mitochondrial dynamics lead to cardiac diseases such as ischemia-reperfusion injury (IRI), heart failure and diabetic cardiomyopathy. Mitochondrial dynamics is determined by mitochondrial fission and fusion proteins, including OPA1, mitofusins and Drp1. These proteins are tightly regulated by a series of signaling pathways through different aspects such as transcription, post translation modifications (PTMs) and proteasome-dependent protein degradation. By modulating these mitochondrial fission and fusion proteins, mitochondria fine-tune their metabolic status to meet the energy demands of the heart. Moreover, these mitochondrial fission and fusion proteins are essential for mediating mitochondrial autophagy (mitophagy), leading to clearance of damaged mitochondria to maintain a healthy population of mitochondria in heart under stressed conditions. Mitochondrial dynamics dependent improvement in mitochondrial metabolism and quality could partially reverse the pathological conditions of heart. This review describes an overview of mechanisms on mitochondrial dynamics regulation and provides potential therapeutic targets for treating cardiovascular diseases.

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.