Curcumin and targeting of molecular and metabolic pathways in multiple sclerosis

Posted on 9 October 2023 by

Abstract

Multiple sclerosis (MS) is a life-threading disease that poses a great threat to the human being lifestyle. Having said extensive research in the realm of underlying mechanisms and treatment procedures, no definite remedy has been found. Over the past decades, many medicines have been disclosed to alleviate the symptoms and marking of MS. Meanwhile, the substantial efficacy of herbal medicines including curcumin must be underscored. Accumulated documents demonstrated the fundamental role of curcumin in the induction of the various signaling pathways. According to evidence, curcumin can play a role in mitochondrial dysfunction and apoptosis, autophagy, and mitophagy. Also, by targeting the signaling pathways AMPK, PGC-1α/PPARγ, and PI3K/Akt/mTOR, curcumin interferes with the metabolism of MS. The anti-inflammatory, antioxidant, and immune regulatory effects of this herbal compound are involved in its effectiveness against MS. Thus, the present review indicates the molecular and metabolic pathways associated with curcumin's various pharmacological actions on MS, as well as setting into context the many investigations that have noted curcumin-mediated regulatory effects in MS.

An in vitro investigation of l‐kynurenine, quinolinic acid, and kynurenic acid on B16 F10 melanoma cell cytotoxicity and morphology

Posted on 9 October 2023 by nCharlise Basson, nJune Cheptoo Serem, nYvette Nkondo Hlophe, nPriyesh Bipathn

Abstract

The metastatic behavior of melanoma has accentuated the need for specific therapy targets. Compounds, namely l-kynurenine ( l-kyn), quinolinic acid (Quin), and kynurenic acid (KA) previously displayed antiproliferative and cytotoxic effects in vitro against cancer cells. Despite the growing interest in these compounds there are limited studies examining the in vitro effects on melanoma. In B16 F10 melanoma cells, RAW 264.7 macrophage cells, and HaCat keratinocyte cells, postexposure to the compounds, crystal violet staining was used to determine the half-maximal inhibitory concentration (IC₅₀), whereas polarization-optical transmitted light differential interference contrast and light microscopy after hematoxylin and eosin (H&E) staining was used to assess morphological changes.  l-kyn, Quin, and KA-induced cytotoxicity in all cell lines, with  l-kyn being the most cytotoxic compound.  l-kyn and KA at IC₅₀-induced morphological changes in B16 F10, RAW 264.7, and HaCat cell lines, whereas Quin had effects on B16 F10 and RAW 264.7 cells but did not affect HaCat cells.  l-kyn, Quin, and KA each display different levels of cytotoxicity, which were cell line specific.  l-kyn was shown to be the most potent compound against all cell lines and may offer future treatment strategies when combined with other viable treatments against melanoma.

Effect of 2‐methoxyestradiol treatment on early‐ and late‐stage breast cancer progression in a mouse model

Posted on 9 October 2023 by

Abstract

The prevalence of breast cancer (BC) continues to increase and is the leading cause of cancer deaths in many countries. Numerous in vitro and in vivo studies have demonstrated that 2-methoxyestradiol (2-ME) has antiproliferative and antiangiogenic effects in BC, thereby inhibiting tumour growth and metastasis. We compared the effect of 2-ME in early- and late-stage BC using a transgenic mouse model—FVB/N-Tg(MMTV-PyVT)—of spontaneously development of aggressive mammary carcinoma with lung metastasis. Mice received 100 mg/kg 2-ME treatment immediately when palpable mammary tumours were identified (early-stage BC; Experimental group 1) and 28 days after palpable mammary tumours were detected (late-stage BC; Experimental group 2). 2-ME was administered via oral gavage three times a week for 28 days after initiation of treatment, whereas control mice received the vehicle containing 10% dimethyl sulfoxide and 90% sunflower oil for the same duration as the treatment group. Mammary tumours were measured weekly over the 28 days and at termination, blood, mammary and lung tissue were collected for analysis. Mice with a tumour volume threshold of 4000 mm³ were killed before the treatment regime was completed. 2-ME treatment of early-stage BC led to lower levels of mammary tumour necrosis, whereas tumour mass and volume were increased. Additionally, necrotic lesions and anti-inflammatory CD163-expressing cells were more frequent in pulmonary metastatic tumours in this group. In contrast, 2-ME treatment of late-stage BC inhibited tumour growth over the 28-day period and resulted in increased CD3+ cell number and tumour necrosis. Furthermore, 2-ME treatment slowed down pulmonary metastasis but did not increase survival of late-stage BC mice. Besides late-stage tumour necrosis, none of the other results were statistically significant. This study demonstrates that 2-ME treatment has an antitumour effect on late-stage BC, however, with no increase in survival rate, whereas the treatment failed to demonstrate any benefit in early-stage BC.

N‐terminal LysSN‐His‐tag improves the production of intracellular recombinant protein in Bacillus subtilis

Posted on 9 October 2023 by

Abstract

Choosing fusion tags to enhance the recombinant protein levels in the cytoplasm of Bacillus subtilis has been limited. Our previous study demonstrated that His-tag at the N-terminus could increase the expression levels of the low-expression gene egfp, while significantly reducing the high-expression genes gfp+ and bgaB in the cytoplasm of B. subtilis. In this study, we aimed to prove the potential of a fusion tag, the combination of the N-terminal domain of B. subtilis lysyl tRNA synthetase (LysSN) and His-tag with varying numbers of histidine (6xHis, 8xHis, 10xHis) by investigating their effects on the expression levels of egfp, gfp+ and bgaB in B. subtilis. For the low-expression gene, LysSN-xHis-tag could enhance the fluorescent intensity of EGFP 23.5 times higher than EGFP without a fusion tag, and 1.5 times higher than that fused with only His-tag. For high-expression genes, the expression level of BgaB and GFP+ was 2.9 and 12.5 times higher than that of His-tag, respectively. The number of histidines in LysSN-xHis-tag did not influence the expression levels of the high-expression genes but affected the expression levels of the low-expression gene.

Effect of lawsone‐preconditioned mesenchymal stem cells on the regeneration of pancreatic β cells in Type 1 diabetic rats

Posted on 9 October 2023 by nJaveria Masnoon, nAisha Ishaque, nIrfan Khan, nAsmat Salim, nNurul Kabirn

Abstract

Diabetes is one of the major health issues globally. Type 1 diabetes mellitus develops due to the destruction of pancreatic β cells. Mesenchymal stem cells (MSCs) having remarkable self-renewal and differentiation potential, can regenerate β cells. MSCs preconditioned with bioactive small molecules possess enhanced biological features and therapeutic potential under in vivo environment. Interestingly, compounds of naphthoquinone class possess antidiabetic and anti-inflammatory properties, and can be explored as potential candidates for preconditioning MSCs. This study analyzed the effect of lawsone-preconditioned human umbilical cord MSCs (hUMSCs) on the regeneration of β cells in the streptozotocin (STZ)-induced Type 1 diabetes (T1D) rats. hUMSCs were isolated and characterized for the presence of surface markers. MSCs were preconditioned with optimized concentration of lawsone. T1D rat model was established by injecting 50 mg/kg of STZ intraperitoneally. Untreated and lawsone-preconditioned hUMSCs were transplanted into the diabetic rats via tail vein. Fasting blood sugar and body weight were monitored regularly for 4 weeks. Pancreas was harvested and β cell regeneration was evaluated by hematoxylin and eosin staining, and gene expression analysis. Immunohistochemistry was also done to assess the insulin expression. Lawsone-preconditioned hUMSCs showed better anti-hyperglycemic effect in comparison with untreated hUMSCs. Histological analysis presented the regeneration of islets of Langerhans with upregulated expression of βcell genes and reduced expression of inflammatory markers. Immunohistochemistry revealed strong insulin expression in the preconditioned hUMSCs compared with the untreated hUMSCs. It is concluded from the present study that lawsone-preconditioned hMSCs were able to exhibit pronounced anti-hyperglycemic effect in vivo compared with hUMSCs alone.

Intracellular calcium ion transients evoked by cell poking independently of released autocrine ATP in Madin–Darby canine kidney cells

Posted on 9 October 2023 by nMinki Chang, nKevin Montagne, nKatsuko S. Furukawa, nTakashi Ushidan

Abstract

The mechanical stimulation induced by poking cells with a glass needle activates Piezo1 receptors and the adenosine triphosphate (ATP) autocrine pathway, thus increasing intracellular Ca²⁺ concentration. The differences between the increase in intracellular Ca²⁺ concentration induced by cell poking and by ATP-only stimulation have not been investigated. In this study, we investigated the Ca²⁺ signaling mechanism induced by autocrine ATP release during Madin–Darby Canine Kidney cell membrane deformation by cell poking. The results suggest that the pathways for supplying Ca²⁺ into the cytoplasm were not identical between cell poking and conventional ATP stimulation. The functions of the G protein-coupled receptor (GPCR) subunits (Gα $\alpha $q, Gβ γ $\beta \gamma $), ATP-activated receptor and the upstream Ca²⁺ release signal from the intracellular endoplasmic reticulum Ca²⁺ store, were investigated. The results show that Gα $\alpha $q plays a major role in the Ca²⁺ response evoked by ATP-only stimulation, while cell poking induces a Ca²⁺ response requiring the involvement of both Gα $\alpha $q and Gβ γ $\beta \gamma $ units simultaneously. These results suggest that GPCR are not only activated by ATP-only stimulation or autocrine ATP release during Ca²⁺ signaling, but also activated by the mechanical effects of cell poking.

Hepatoprotective effect of p‐Coumaric acid against KBrO3‐induced apoptosis in HepG2 cells

Posted on 9 October 2023 by

Abstract

In the present study, we investigated the effect of the p-Coumaric acid (PCA), a phenolic acid, on potassium bromate (KBrO₃) induced oxidative damage, Ras/Raf/MEK signaling, and apoptosis in HepG2 cells. Our findings showed that PCA-treated cells prevented cytotoxicity compared with KBrO_3-treated cells. Furthermore, KBrO₃-induced oxidative stress and lipid peroxidation was attenuated by PCA and it also increased the antioxidant levels such as SOD, CAT, and GPX. Additionally, PCA inhibited the KBrO₃-induced DNA damage in HepG2 cells. Moreover, PCA treatment suppressed the activation of Ras/Raf/MEK signaling and increased the expression of PRDX-1. In addition, PCA prevented the KBrO₃-induced apoptosis cascade by altering the expression of proapoptotic, Bax, caspase-3, and antiapoptotic, Bcl-2 proteins. The present study proves that PCA inhibited the KBrO₃-induced oxidative stress, DNA damage, and apoptotic signaling cascade in HepG2 cells.

Recent Point of Care (PoC) Electrochemical Testing Trends of New Diagnostics Platforms for Vitamin D

Posted on 9 October 2023 by nMervenur Kirazoğlu, nBirgül Benlin

Electrochemical sensors, which offer great performance with inexpensive additives, appeal to all market groups, allow the detection of vitamins, will likely continue to improve, and become a significant part of daily life in the future. This review explained why we think it will be life-changing, a few application areas that we think will have an immediate impact on nanosensing opportunities.

Abstract

Recent advancements in electrochemical sensors for the detection of vitamins, particularly vitamin D, have drawn a lot of attention due to their outstanding advantages of simplicity and high sensitivity. For the purpose of detecting vitamin D in this circumstance, recent research has focused on developing electrochemical sensors. Although there is always space for improvement, electrochemical sensors for vitamin D detection and its transformation into point-of-care devices have made great strides lately. For example, the development of innovative electrode materials that can increase sensitivity and selectivity continues to garner a lot of interest. New suggestions on adsorptive detections using vitamin D carriers like nanoclays or hydroxyapatite-clay composites are being developed. These biosensors hold huge potential for the detection of cheap, disposable, and biodegradable solutions. Also, the biosensor could monitor the depletion of vitamin levels, providing a real-time platform for the Internet of Medical Things, fifth-generation wireless communications, and smartphone-based electrochemical sensors. Currently, electrochemical sensors based on smartphones have been proposed to detect using various biomarkers for monitoring several changes in glucose, etc. We believe smartphone-based electrochemical sensors and adsorptive sensing platforms provides a novel way toward point-of-care tests for identifying especially vitamin D deficiency and real-time monitoring

Cover Picture: (ChemistrySelect 38/2023)

Posted on 9 October 2023 by Wiley: ChemistrySelect: Table of Contents

Applications of Highly Stable Silver Nanoparticles from Garcinia mangostana Pericarp Extract: Bioactivities, Catalysis, and Optical Sensing

Posted on 9 October 2023 by

This study demonstrates the benefits of green synthesis of silver nanoparticles (AgNPs) from Garcinia mangostana pericarp extract for multiple applications in bioactivities, catalysis, and sensing. This implies and orients the various practices of AgNPs and evidence of the great potential of the green chemistry pathway.

Abstract

In this work, the Garcinia mangostana pericarp aqueous extract was utilized as an efficient reducing agent for the phyto-synthesis of eco-friendly silver nanoparticles (GM/AgNPs (GMAs)). Characterization of the as-synthesized material revealed the optimal synthesis conditions of 1 mL of the extract, 1.6 mL of AgNO₃, and 1 mL of pH 10 buffer solution at 70 °C for 30 min of reaction. The formation and distribution of quasi-spherical silver nanoparticles were elucidated with an average particle size of 22.12±1.106 nm, whilst the colloidal system of GMAs also possessed a negative surface charge (−25.4 mV) with such low particle instability parameters (PIP), signifying great stability even after 8 weeks. Furthermore, the material demonstrated excellent bioactivities, wherein a good inhibitory was acquired towards both P. aeruginosa and S. aureus. Besides, the synthesized GMAs provided great catalytic reduction performances, which removed 98.75, 96.55, and 90.85 % of RhB, MO, and 4-NP, respectively, within 120 s. Along with a low detection limit for surveyed heavy metal ions as well as H₂O₂ in specific concentration ranges, the phyto-synthesized GMAs can be efficaciously employed in a wide range of environmental applications, namely in the medical and wastewater remediation sectors.