The role of glycans in the mechanobiology of cancer.

Although cancer is a genetic disease, physical changes such as stiffening of the extracellular matrix also commonly occur in cancer. Cancer cells sense and respond to extracellular matrix stiffening through the process of mechanotransduction. Cancer cell mechanotransduction can enhance cancer-promoting cell behaviors such as survival signaling, proliferation, and migration. Glycans, carbohydrate-based polymers, have recently emerged as important mediators and/or modulators of cancer cell mechanotransduction. Stiffer tumors are characterized by increased glycan content on cancer cells and their associated extracellular matrix. Here we review the role of cancer-associated glycans in coupled mechanical and biochemical alterations during cancer progression. We discuss the recent evidence on how increased expression of different glycans, in the form of glycoproteins and proteoglycans, contributes to both mechanical changes in tumors and corresponding cancer cell responses. We conclude with a summary of emerging tools that can be used to modify glycans for future studies in cancer mechanobiology.

Investigating the protective role of metformin on lithium-induced hypothyroidism.

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li-induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T3 and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T4 level (up to 2.1 ng/ml). Also, a significant reduction in Li-related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co-administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.

Mercury Exposure and Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Methods: Scopus and PubMed databases were systematically searched from their inception to November 2021 to obtain pertinent studies. Standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the difference in Hg levels between people with and without T2DM. The association of the Hg exposure with T2DM was assessed using a random-effects model by pooling the odds ratios (ORs) and 95% CIs. Results: A total of 17 studies, with 42,917 participants, aged ≥18 years, were analyzed. Overall, Hg levels were significantly higher in T2DM patients compared with non-T2DM controls (SMD = 1.07; 95%CI = 0.59 to 1.55, P ≤ 0.001), with significant heterogeneity across studies (I2 = 96.1%; P=≤0.001). No significant association was found between Hg exposure and risk of T2DM in the overall analysis and subgroup analysis based on the source of sample and study design. However, higher exposure to Hg was related to reduced risk of T2DM in men (OR = 0.71; 95%CI = 0.57 to 0.88), but not in women. No significant evidence for publication bias was detected. Conclusions: Although the Hg level in T2DM is significantly higher than that of nondiabetics, there was no association between Hg exposure and the overall risk of T2DM. Nevertheless, our study shows that higher exposure to Hg might reduce the risk of T2DM in men.

Carbon-based Nanomaterials and Curcumin: A Review of Biosensing Applications.

Curcumin, the main active constituent of turmeric (Curcuma longa L.), is a naturally occurring phenolic compound with a wide variety of pharmacological activities. Although it has multiple pharmaceutical properties, its bioavailability and industrial usage are hindered due to rapid hydrolysis and low water solubility. Due to the growing market of curcumin, exact determination of curcumin in trade and human biological samples is important for monitoring therapeutic actions. Different nanomaterials have been suggested for sensing curcumin; and in this case, carbon-based nanomaterials (CNMs) are one of the most outstanding developments in nanomedicine, biosensing, and regenerative medicine. There are a considerable number of reports which have shown interesting potential of CNMs-based biosensors in the sensitive and selective detection of curcumin. Therefore, this review aims to increase understanding the interaction of curcumin with CNMs in the context of biosensing.

Curcumin: a phytochemical modulator of estrogens and androgens in tumors of the reproductive system.

Curcumin (Cur) is an active derivative extracted from turmeric which exerts a wide range of interactions with biomolecules through complex signaling pathways. Cur has been extensively shown to possess potential antitumor properties. In addition, there is growing body of evidence suggesting that Cur may exert potential anti-estrogen and anti-androgen activity. In vitro and in vivo studies suggest that anticancer properties of Cur against tumors affecting the reproductive system in females and males may be underlied by the Cur-mediated inhibition of androgen and estrogen signaling pathways. In this review we examine various studies assessing the crosstalk between Cur and both androgen and estrogen hormonal activity. Also, we discuss the potential chemopreventive and antitumor role of Cur in the most prevalent cancers affecting the reproductive system in females and males.

Curcumin: A naturally occurring autophagy modulator.

Autophagy is a self-degradative process that plays a pivotal role in several medical conditions associated with infection, cancer, neurodegeneration, aging, and metabolic disorders. Its interplay with cancer development and treatment resistance is complicated and paramount for drug design since an autophagic response can lead to tumor suppression by enhancing cellular integrity and tumorigenesis by improving tumor cell survival. In addition, autophagy denotes the cellular ability of adapting to stress though it may end up in apoptosis activation when cells are exposed to a very powerful stress. Induction of autophagy is a therapeutic option in cancer and many anticancer drugs have been developed to this aim. Curcumin as a hydrophobic polyphenol compound extracted from the known spice turmeric has different pharmacological effects in both in vitro and in vivo models. Many reports exist reporting that curcumin is capable of triggering autophagy in several cancer cells. In this review, we will focus on how curcumin can target autophagy in different cellular settings that may extend our understanding of new pharmacological agents to overcome relevant diseases.

Carbon nanomaterials and amyloid-beta interactions: potentials for the detection and treatment of Alzheimer's disease?

Carbon-based nanomaterials have unique physicochemical properties relevant to the diagnosis and treatment of various diseases. There have been many reports indicating that carbon nanomaterials (CNMs) can interact and perturb biomolecules such as proteins and amyloid structures. This review is an attempt to reflect the role of CNMs in the treatment and detection of Alzheimer's disease (AD). The potential of CNMs in the field of neuroscience has also been reviewed. The exposure to CNMs ends up with effective radical and peptide scavenging structures, which, in turn, inhibit further formation and progression of amyloid fibrils. However, the effect of CNMs on initial nucleation and lag phase in this process may promote fibrillation. We have discussed the controversy that whether CNMs promote or inhibit the formation of amyloid beta (Aß) fibrils to help preventing their toxicity or enhancing their therapeutic effects.

Biomedical applications of carbon nanomaterials: Drug and gene delivery potentials.

One of the major components in the development of nanomedicines is the choice of the right biomaterial, which notably determines the subsequent biological responses. The popularity of carbon nanomaterials (CNMs) has been on the rise due to their numerous applications in the fields of drug delivery, bioimaging, tissue engineering, and biosensing. Owing to their considerably high surface area, multifunctional surface chemistry, and excellent optical activity, novel functionalized CNMs possess efficient drug-loading capacity, biocompatibility, and lack of immunogenicity. Over the past few decades, several advances have been made on the functionalization of CNMs to minimize their health concerns and enhance their biosafety. Recent evidence has also implied that CNMs can be functionalized with bioactive peptides, proteins, nucleic acids, and drugs to achieve composites with remarkably low toxicity and high pharmaceutical efficiency. This review focuses on the three main classes of CNMs, including fullerenes, graphenes, and carbon nanotubes, and their recent biomedical applications.

Protective effects of curcumin against aflatoxicosis: A comprehensive review.

Aflatoxicosis is a deleterious medical condition that results from aflatoxins (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental effects on the liver, kidneys, reproductive organs, and also on immunological and cardiovascular systems. Aflatoxicosis is closely associated with overproduction of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The main target organ for AF toxicity is the liver, where DNA adducts, degranulation of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion, mitochondrial dysfunction, and reduction of enzymatic and non-enzymatic antioxidants are manifestations of aflatoxicosis. Curcuma longa L. (turmeric) is a medicinal plant widely utilized all over the world for culinary and phytomedical purposes. Considering the antioxidant characteristic of curcumin, the main active component of turmeric, this review is intended to critically summarize the available evidence supporting possible effectiveness of curcumin against aflatoxicosis. Curcumin can serve as a promising candidate for attenuation of the adverse consequences of aflatoxicosis, acting mainly through intrinsic antioxidant effects aroused from its structure, modulation of the immune system as reflected by interleukin-1ß and transforming growth factor-ß, and interfering with AF's biotransformation by cytochrome P450 isoenzymes CYP1A, CYP3A, CYP2A, CYP2B, and CYP2C.

Berberine: A potential adjunct for the treatment of gastrointestinal cancers?

Gastrointestinal cancers are among the most prevalent cancers in the general population. Despite effective early diagnostics and intervention, the gastrointestinal cancer-related mortality still remains elevated. Berberine (BBR) is a benzyl tetra isoquinoline alkaloid exracted from several plants. BBR is nontoxic to human normal cells, but suppresses the growth of different tumor cells: melanoma, epidermoid carcinoma, hepatoma, oral carcinoma, glioblastoma, prostatic carcinoma, and gastric carcinoma. In particular, BBR seems to suppress the proliferation of gastrointestinal cancers in a number of preclinical models. Several mechanisms of action have been hypothesized and demonstrated: immunomodulation, inhibition of topoisomerase enzymes, suppression of the EGF receptor, Her2/neu, and the VEGF receptor, induction of p53, Cip1/p21, Kip1/p27, Rb expression, induction of apoptosis (by regulation of MMPs pathway, caspases, Bax, and Smac/DIABLO), inhibition of arylamin N-acetyltransferase activity, and regulation of microRNAs expression. The aim of this review is to summarize the pharmacological effects of BBR on animal and human gastrointestinal cancers.

The significance of clinicopathological aspects of tumor for the detection of liver micrometastasis in patients with colorectal cancer.

BACKGROUND: Colorectal tumor is one of the main causes of death in our country. The aim of the present study was to determine the clinicopathological aspects of tumor and the presence of hepatic micrometastasis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Forty two patients with CRC were evaluated in the study surgical treatment was performed and liver biopsy was taken for the evaluation of micrometastasis by immunohistochemistry and polymerase chain reaction. The variables that have been evaluated were: Patient's gender, patients age at the time of diagnosis, size and location of tumor, tumor-node-metastasis stage and grade of the primary tumor, lymph node involvement, lymphovascular and neural invasion, presence of macrometastasis and carcinoembryonic antigen level prior to surgery. After 1 year patients were called and asked to come back to the clinic for elective colonoscopy to evaluate the surgical site for recurrence of tumor and survival. All variables were compared between patients in whom liver micrometastasis were present in comparison with patients without liver micrometastasis. RESULTS: Of the studied patients (6 with positive micrometatsis and 36 without micrometstasis), 38 were alive after 1 year (6 with positive micrometatsis and 32 without micrometstasis) and the difference was not significant between groups with or without micrometastasis (P = 0.52). In four of survived patients colonoscopy was abnormal, however this difference was not also significant between groups (P = 0.59). CONCLUSION: Clinicopathologic aspect of tumor was not different in CRC patients with and without hepatic micrometastasis.

PEGylated Pemetrexed and PolyNIPAM Decorated Gold Nanoparticles: A Biocompatible and Highly Stable CT Contrast Agent for Cancer Imaging.

This study describes a multifunctional nanoparticle platform for targeted CT imaging and therapy of cancers. Pemetrexed (conjugated with polyethylene glycol, MW 2000 Da) and polyNIPAM (PEGylated) were designed for targeted delivery to folate receptors and thermally ablated tumors, respectively. These moieties were coated on gold nanoparticles (7 and 30 nm), and the prepared compounds were characterized using 1H NMR, FT-IR, CHNS, DLS, TEM, TGA, and UV-vis. The resulting agents exhibited 2-4 times higher X-ray attenuation compared to Visipaque and demonstrated specific accumulation in tumor tissue (4T1 xenograft model) 90 min after injection in mice. The nanoparticles displayed anticancer activity against 4T1 and MDA-MB-231 breast cancer cells (IC50: 182.87 and 206.18 µg/mL) and good biocompatibility. Importantly, the platform showed excellent stability over a year and at pH 2-12 and temperature range of -78 to 40 °C, and a water-dichloromethane extraction method was optimized for efficient purification, facilitating large-scale production.

Dynamic Adaptation in Extant Porins Facilitates Antibiotic Tolerance in Energetic Escherichia coli.

Bacteria can tolerate antibiotics despite lacking the genetic components for resistance. The prevailing notion is that tolerance results from depleted cellular energy or cell dormancy. In contrast to this view, many cells in the tolerant population of Escherichia coli can exhibit motility - a phenomenon that requires cellular energy, specifically, the proton-motive force (PMF). As these motile-tolerant cells are challenging to isolate from the heterogeneous tolerant population, their survival mechanism is unknown. Here, we discovered that motile bacteria segregate themselves from the tolerant population under micro-confinement, owing to their unique ability to penetrate micron-sized channels. Single-cell measurements on the motile-tolerant population showed that the cells retained a high PMF, but they did not survive through active efflux alone. By utilizing growth assays, single-cell fluorescence studies, and chemotaxis assays, we showed that the cells survived by dynamically inhibiting the function of existing porins in the outer membrane. A drug transport model for porin-mediated intake and efflux pump-mediated expulsion suggested that energetic tolerant cells withstand antibiotics by constricting their porins. The novel porin adaptation we have uncovered is independent of gene expression changes and may involve electrostatic modifications within individual porins to prevent extracellular ligand entry.

Successful auto-implantation of hepatic cells in lung tissue: An animal study.

BACKGROUND: This study was proposed to evaluate a new method for autograft transplantation of liver tissue fragments (LTF) in the lung parenchyma and bronchus of dogs and to compare the results to find out if they are suitable sites for hepatocyte implantation or not. MATERIALS AND METHODS: THE DOGS WERE RANDOMLY ASSIGNED INTO TWO CATEGORIES: LTF auto-transplantation to the lung parenchyma and into the bronchus. The suspensions of normal saline and LTF were injected and implanted into the lung parenchyma and the main bronchus of the right accessory lobe in first and second groups, respectively. Two weeks later the right accessory lobe was removed and sent for a histopathological study. All samples were checked under a light microscope with regard to the presence of hepatocytes, with both the Hematoxylin and Eosin (H and E) preparation and immunohistochemistry (IHC) method, using a CK-18 marker. All results were double-checked with a polymerase chain reaction (PCR). RESULTS: The mean weight of all the dogs was 19.87 ± 0.93 kg and mean age was 3.58 ± 0.31 years. After 15 days, the H and E, IHC, and PCR studies revealed that in the first group, all the dogs (n = 4) had living liver tissue, which survived in the lung parenchyma successfully. In contrast, none of the dogs (n = 0) in the second group showed surviving hepatocytes in the bronchus (P < 0.001). CONCLUSION: Implantation of the LTFs into the lung parenchyma could be a source of hepatic cell production.

One-Step Preparation of Luteolin Nanoemulsion and Evaluation of its Anti-inflammatory Effect in Animal Models.

BACKGROUND: Nanoemulsions are promising drug delivery systems for topical application owing to the high transdermal penetration. OBJECTIVE: Due to the side effects of existing anti-inflammatory drugs, much attention has been paid to natural products such as flavonoids. The aim of this work was to formulate luteolin nanoemulsion (LNE) and to evaluate its anti-inflammatory effect. METHODS: LNE was prepared using the low-energy spontaneous emulsion method and characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS). The anti-inflammatory effect of LNE was assessed in formalin and acetic acid-induced inflammation methods (Whittle test). Treatment with LNE (i.p, 4 consecutive days, 40 mg/kg) was compared with diclofenac 25 mg/kg and normal saline. In the formalin test, data were recorded at 1, 2 and 4 hours after formalin injection and in the Wittle test, the extent of Evans blue leakage in the peritoneal cavity was considered as vascular permeability. RESULTS: Formalin-induced edema decreased in the LNE group, but this reduction was not significant (p > 0.05), however, in Whittle test, both LNE and diclofenac significantly reduced Evans blue leakage compared with the group treated with acetic acid alone (p < 0.05). CONCLUSION: Our results confirm the anti-inflammatory effect of LNE and give up a new platform for the design and development of bio-based carriers for more successful drug delivery.

Cell encapsulation in alginate-based microgels using droplet microfluidics; a review on gelation methods and applications.

Cell encapsulation within the microspheres using a semi-permeable polymer allows the two-way transfer of molecules such as oxygen, nutrients, and growth factors. The main advantages of cell encapsulation technology include controlling the problems involved in transplanting rejection in tissue engineering applications and reducing the long-term need for immunosuppressive drugs following organ transplantation to eliminate the side effects. Cell-laden microgels can also be used in 3D cell cultures, wound healing, and cancerous clusters for drug testing. Since cell encapsulation is used for different purposes, several techniques have been developed to encapsulate cells. Droplet-based microfluidics is one of the most valuable techniques in cell encapsulating. This study aimed to review the geometries and the mechanisms proposed in microfluidic systems to precisely control cell-laden microgels production with different biopolymers. We also focused on alginate gelation techniques due to their essential role in cell encapsulation applications. Finally, some applications of these microgels and researches will be explored.

Diosgenin: Mechanistic Insights on its Anti-inflammatory Effects.

Diosgenin (DG), a well-known steroid saponin, has shown anti-inflammatory effects. This review was aimed to discuss all published literature concerning the anti-inflammatory effects of diosgenin. Based on the modulatory impact of DG on the NF-κB pathway, its supplementation is associated with downregulation of the NF-κB pathway and TGF-ß, resulting in inhibition of inflammation. It appears that upstream modulators of NF-κB signaling pathways such as Tlrs and downstream mediators include iNOS and COX-2, leading to the inhibition of the inflammatory response and development of pathological conditions. Due to the low toxicity of the herbal compounds, the risk of the side effects of DG use for the management of inflammatory disorders such as asthma, rheumatism, rhinitis, and arthritis is lower than that of synthetic glucocorticoids. It has been shown that regulation of NF-κB and oxidative stress signaling pathways by DG is beneficial against cardiotoxicity induced by chemotherapeutic agents such as doxorubicin.

A review on in vitro/in vivo response of additively manufactured Ti-6Al-4V alloy.

Bone replacement using porous and solid metallic implants, such as Ti-alloy implants, is regarded as one of the most practical therapeutic approaches in biomedical engineering. The bone is a complex tissue with various mechanical properties based on the site of action. Patient-specific Ti-6Al-4V constructs may address the key needs in bone treatment for having customized implants that mimic the complex structure of the natural tissue and diminish the risk of implant failure. This review focuses on the most promising methods of fabricating such patient-specific Ti-6Al-4V implants using additive manufacturing (AM) with a specific emphasis on the popular subcategory, which is powder bed fusion (PBF). Characteristics of the ideal implant to promote optimized tissue-implant interactions, as well as physical, mechanical/chemical treatments and modifications will be discussed. Accordingly, such investigations will be classified into 3B-based approaches (Biofunctionality, Bioactivity, and Biostability), which mainly govern native body response and ultimately the success in implantation.

Standard oral rehydration solution as a new storage medium for avulsed teeth.

OBJECTIVES: Immediate tooth replantation is the choice of treatment in tooth avulsion. When it is impossible to replant immediately an appropriate medium must be used to maintain periodontal ligament (PDL) cell viability. The purpose of this study was to investigate the effect of standard Oral Rehydration Solution (ORS) as a new storage medium for the preservation of PDL cell viability. METHODS: 75 young adult premolar teeth without periodontal disease were used (25 teeth for each medium). Teeth were placed in the experimental media including standard ORS, HBSS and tap water for intended incubation periods. After that, PDL cells were separated and cell viability was determined by Trypan blue staining. The results were analysed by one way ANOVA. RESULTS: There was no significant difference between HBSS and Standard ORS in supporting the maintenance of PDL cell viability. A significant difference between the effect of Standard ORS and water and HBSS and water was observed in maintaining PDL cell viability. CONCLUSIONS: Standard ORS is a suitable transport medium to support the maintenance of PDL cell viability. Regarding its inexpensiveness and availability, standard ORS has preference over some other approved transport media like HBSS.

Sol-Gel Synthesis, Physico-Chemical and Biological Characterization of Cerium Oxide/Polyallylamine Nanoparticles.

Cerium oxide nanoparticles (CeO2-NPs) have great applications in different industries, including nanomedicine. However, some studies report CeO2-NPs-related toxicity issues that limit their usage and efficiency. In this study, the sol-gel method was applied to the synthesis of CeO2-NPs using poly(allylamine) (PAA) as a capping and/or stabilizing agent. The different molecular weights of PAA (15,000, 17,000, and 65,000 g/mol) were used to investigate the physico-chemical and biological properties of the NPs. In order to understand their performance as an anticancer agent, three cell lines (MCF7, HeLa, and erythrocyte) were analyzed by MTT assay and RBC hemolysis assay. The results showed that the CeO2-NPs had anticancer effects on the viability of MCF7 cells with half-maximal inhibitory concentration (IC50) values of 17.44 ± 7.32, 6.17 ± 1.68, and 0.12 ± 0.03 µg/mL for PAA15000, PAA17000, PAA65000, respectively. As for HeLa cells, IC50 values reduced considerably to 8.09 ± 1.55, 2.11 ± 0.33, and 0.20 ± 0.01 µg/mL, in order. A decrease in the viability of cancer cells was associated with the 50% hemolytic concentration (HC50) of 0.022 ± 0.001 mg/mL for PAA15000, 3.74 ± 0.58 mg/mL for PAA17000, and 7.35 ± 1.32 mg/mL for PAA65000. Ultraviolet-Visible (UV-vis) spectroscopy indicated that an increase in the PAA molecular weight led to a blue shift in the bandgap and high amounts of Ce3+ on the surface of the nanoceria. Thus, PAA65000 could be considered as a biocompatible nanoengineered biomaterial for potential applications in cancer nanomedicine.