Malaysia is experiencing an encouraging socio-economic development, especially in its
quest towards Vision 2020 and achieving the status as a developed country. The success can be
attributed to the government’s efforts and commitment in developing projects, which include the
construction of new townships and public infrastructures. Through the implementation of
Environmental Management Plan (EMP) during the construction phase, the government has taken
great efforts and initiatives to ensure that construction projects are well-developed in a sustainable
manner. Unfortunately, these rapid physical developments affect and pollute the surrounding
environment, even though EMP is implemented at the construction site. The effectiveness of
sustainable construction methods in the plan has been found to be very limited in the actual industrial
practice. Hence, this paper aims to determine the important criteria needed to be incorporated into
EMP in enhancing and ensuring its effectiveness in managing environmental aspects during the
construction stage.
Research implementation methodology is an important element in any study. Good data
are obtained from the study that is carefully planned based on an appropriate design, as well as the
approach that is used in the process of obtaining the data. The main objective of the proposed study is
to identify criteria for sustainable construction. Therefore, the right selection of study design and
implementation methodology is very important to ensure that the objectives are successfully achieved.
This manuscript writing presents the description of the design and implementation methodology used
in this study, namely content analysis, to meet the objective. Justification for the selected method to
achieve the objectives of the study is also discussed.
Selection of a suitable and appropriate method is an important aspect in ensuring successful
implementation of a research. The proposed study aims to obtain weights for sustainable construction
criteria from the input and perception of industrial practitioner, and also to explore their opinion on
the criteria. Therefore, the selection and use of study implementation method will determine the
direction of the study whether the intended objectives can be achieved. This manuscript writing presents
the description of the structured interview used to obtain and collect the required data. The suitability
and implementation of the methods have been described in this study, in which the ultimate aim of its
application is to ensure that the collected data is meaningful to the study.
Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.
The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.
Alcohol use disorder (AUD) has been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Prolonged excessive alcohol intake contributes to increased production of reactive oxygen species that triggers neuroimmune response and cellular apoptosis and necrosis via lipid peroxidation, mitochondrial, protein or DNA damage. Long term binge alcohol consumption also upregulates glutamate receptors, glucocorticoids and reduces reuptake of glutamate in the central nervous system, resulting in glutamate excitotoxicity, and eventually mitochondrial injury and cell death. In this review, we delineate the following principles in alcohol-induced neurodegeneration: (1) alcohol-induced oxidative stress, (2) neuroimmune response toward increased oxidants and lipopolysaccharide, (3) glutamate excitotoxicity and cell injury, and (4) interplay between oxidative stress, neuroimmune response and excitotoxicity leading to neurodegeneration and (5) potential chronic alcohol intake-induced development of neurodegenerative diseases, including Alzheimer's and Parkinson's disease.
Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% v/v) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.
Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.
Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.
The field of nanomedicine has provided a fresh approach to cancer treatment by addressing the limitations of current therapies and offering new perspectives on enhancing patients' prognoses and chances of survival. Chitosan (CS) is isolated from chitin that has been extensively utilized for surface modification and coating of nanocarriers to improve their biocompatibility, cytotoxicity against tumor cells, and stability. HCC is a prevalent kind of liver tumor that cannot be adequately treated with surgical resection in its advanced stages. Furthermore, the development of resistance to chemotherapy and radiotherapy has caused treatment failure. The targeted delivery of drugs and genes can be mediated by nanostructures in treatment of HCC. The current review focuses on the function of CS-based nanostructures in HCC therapy and discusses the newest advances of nanoparticle-mediated treatment of HCC. Nanostructures based on CS have the capacity to escalate the pharmacokinetic profile of both natural and synthetic drugs, thus improving the effectiveness of HCC therapy. Some experiments have displayed that CS nanoparticles can be deployed to co-deliver drugs to disrupt tumorigenesis in a synergistic way. Moreover, the cationic nature of CS makes it a favorable nanocarrier for delivery of genes and plasmids. The use of CS-based nanostructures can be harnessed for phototherapy. Additionally, the incur poration of ligands including arginylglycylaspartic acid (RGD) into CS can elevate the targeted delivery of drugs to HCC cells. Interestingly, smart CS-based nanostructures, including ROS- and pH-sensitive nanoparticles, have been designed to provide cargo release at the tumor site and enhance the potential for HCC suppression.
Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.
Brain tumors, which are highly malignant, pose a significant threat to health and often result in substantial rates of mortality and morbidity worldwide. The brain cancer therapy has been challenging due to obstacles such as the BBB, which hinders effective delivery of therapeutic agents. Additionally, the emergence of drug resistance further complicates the management of brain tumors. TMZ is utilized in brain cancer removal, but resistance is a drawback. ncRNAs are implicated in various diseases, and their involvement in the cancer is particularly noteworthy. The focus of the current manuscript is to explore the involvement of ncRNAs in controlling drug resistance, specifically in the context of resistance to the chemotherapy drug TMZ. The review emphasizes the function of ncRNAs, particularly miRNAs, in modulating the growth and invasion of brain tumors, which significantly influences their response to TMZ treatment. Through their interactions with various molecular pathways, miRNAs are modulators of TMZ response. Similarly, lncRNAs also associate with molecular pathways and miRNAs, affecting the efficacy of TMZ chemotherapy. Given their functional properties, lncRNAs can either induce or suppress TMZ resistance in brain tumors. Furthermore, circRNAs, which are cancer controllers, regulate miRNAs by acting as sponges, thereby impacting the response to TMZ chemotherapy. The review explores the correlation between ncRNAs and TMZ chemotherapy, shedding light on the underlying molecular pathways involved in this process.
Hydrogels represent intricate three-dimensional polymeric structures, renowned for their compatibility with living systems and their ability to naturally degrade. These networks stand as promising and viable foundations for a range of biomedical uses. The practical feasibility of employing hydrogels in clinical trials has been well-demonstrated. Among the prevalent biomedical uses of hydrogels, a significant application arises in the context of wound healing. This intricate progression involves distinct phases of inflammation, proliferation, and remodeling, often triggered by trauma, skin injuries, and various diseases. Metabolic conditions like diabetes have the potential to give rise to persistent wounds, leading to delayed healing processes. This current review consolidates a collection of experiments focused on the utilization of hydrogels to expedite the recovery of wounds. Hydrogels have the capacity to improve the inflammatory conditions at the wound site, and they achieve this by diminishing levels of reactive oxygen species (ROS), thereby exhibiting antioxidant effects. Hydrogels have the potential to enhance the growth of fibroblasts and keratinocytes at the wound site. They also possess the capability to inhibit both Gram-positive and Gram-negative bacteria, effectively managing wounds infected by drug-resistant bacteria. Hydrogels can trigger angiogenesis and neovascularization processes, while also promoting the M2 polarization of macrophages, which in turn mitigates inflammation at the wound site. Intelligent and versatile hydrogels, encompassing features such as pH sensitivity, reactivity to reactive oxygen species (ROS), and responsiveness to light and temperature, have proven advantageous in expediting wound healing. Furthermore, hydrogels synthesized using environmentally friendly methods, characterized by high levels of biocompatibility and biodegradability, hold the potential for enhancing the wound healing process. Hydrogels can facilitate the controlled discharge of bioactive substances. More recently, there has been progress in the creation of conductive hydrogels, which, when subjected to electrical stimulation, contribute to the enhancement of wound healing. Diabetes mellitus, a metabolic disorder, leads to a slowdown in the wound healing process, often resulting in the formation of persistent wounds. Hydrogels have the capability to expedite the healing of diabetic wounds, facilitating the transition from the inflammatory phase to the proliferative stage. The current review sheds light on the biological functionalities of hydrogels, encompassing their role in modulating diverse mechanisms and cell types, including inflammation, oxidative stress, macrophages, and bacteriology. Additionally, this review emphasizes the significance of smart hydrogels with responsiveness to external stimuli, as well as conductive hydrogels for promoting wound healing. Lastly, the discussion delves into the advancement of environmentally friendly hydrogels with high biocompatibility, aimed at accelerating the wound healing process.