Biosynthesis of palladium, platinum, and their bimetallic nanoparticles using rosemary and ginseng herbal plants: evaluation of anticancer activity.

In this research, palladium (II) and platinum (II), as well as their bimetallic nanoparticles were synthesized using medicinal plants in an eco-friendly manner. Rosemary and Ginseng extracts were chosen due to their promising anticancer potential. The synthesized nanoparticles underwent characterization through FT-IR spectroscopy, DLS, XRD, EDX, SEM, and TEM techniques. Once the expected structures were confirmed, the performance of these nanoparticles, which exhibited an optimal size, was evaluated as potential anticancer agents through in vitro method on colon cancer cell lines (Ls180, SW480). MTT assay studies showed that the synthesized nanoparticles induced cell death. Moreover, real-time PCR was employed to investigate autophagy markers and the effect of nanoparticles on the apoptosis process, demonstrating a significant effect of the synthesized compounds in this regard.

On chip synthesis of a pH sensitive gefitinib anticancer drug nanocarrier based on chitosan/alginate natural polymers.

In this research, using a microfluidic chip, a nanocarrier for the anticancer drug gefitinib was synthesized. Chitosan and alginate natural polymers were utilized for the synthesis of the nanocarrier. The synthesis of the nanocarrier comprises the interaction of secondary amine functional groups of gefitinib molecules with carboxylate functional groups of alginate polymer to form the primary nucleus followed by the formation of the nanocarrier through the self-assembly of chitosan and alginate polymers on a fabricated microfluidic chip. The chip was fabricated by laser engraving poly(methyl methacrylate) polymer sheets. The nanocarrier was characterized by FT-IR, DLS, SEM, and TEM techniques. The synthesized nanocarrier had a size distribution of 5.30 ± 2.60 nm and the encapsulation efficiency percent was 68.4% in the optimum conditions. The loading efficiency was calculated as 50.2 mg g-1 of nanocarrier. Drug release studies showed that the nanocarrier is sensitive to pH and releases more gefitinib in acidic environments. Cytotoxicity of the synthesized nanocarrier was studied on the A549 non-small cell lung cancer, and the MTT test showed that the synthesized nanocarrier has a lower IC50 value than the free drug. Also, the cytotoxicity studies showed that the materials used for the synthesis of nanocarrier do not show significant cytotoxicity. Compared to the previously reported method, the developed microfluidic-assisted method showed advantages such as a faster synthesis procedure and comparable encapsulation efficiency and loading capacity.

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

Aerosol assisted synthesis of a pH responsive curcumin anticancer drug nanocarrier using chitosan and alginate natural polymers.

In recent years, several nanocarrier synthesis methods have been developed. In cancer therapy, the use of smart nanocarriers is of interest. Smart nanocarriers respond to their environment and can release their cargo in a controlled manner under the action of internal or external stimuli. In this work, we report on the development of an aerosol-assisted method for the synthesis of curcumin-loaded chitosan/alginate-based polymeric nanocarrier (CurNCs). A custom-fabricated multi-nebulizer system was utilized for the synthesis of CurNCs. The developed system comprises three main parts a sprayer, an electric heater tunnel, and a collector. Curcumin and chitosan solutions were sprayed using a pneumatic multinebulizer into the electric heater tunnel to form chitosan-curcumin assemblies. Then, the aerosol was guided into the collector solution containing sodium alginate and tri-poly phosphate aqueous solution for further cross-linkage. The synthesized CurNCs were characterized using TEM, DLS, and FTIR techniques. The TEM size of the nanoparticles was 8.62 ± 2.25 nm. The release experiments revealed that the nanocarrier is sensitive to the environment pH as more curcumin is released at acidic pH values (as is the case for cancerous tissues) compared to physiological pH. The curcumin content of the nanocarrier was 77.27 mg g-1 with a drug loading efficiency of 62%. The in-vitro cytotoxicity of the synthesized nanocarrier was evaluated against the MCF7 breast cancer cell line. The IC50 concentrations for CurNCs and curcumin were obtained as 14.86 and 16.45 mg mL-1, respectively. The results showed that while the empty nanocarrier shows non-significant cytotoxicity, the CurNCs impact the cell culture and cause prolonged cell deaths. Overall, pH-responsive curcumin polymeric nanocarrier was synthesized using a custom fabricated aerosol-based method. The method enabled fast and feasible synthesis of the nanocarrier with high efficiency.

Epigenetic regulation of autophagy in gastrointestinal cancers.

The development of novel therapeutic approaches is necessary to manage gastrointestinal cancers (GICs). Considering the effective molecular mechanisms involved in tumor growth, the therapeutic response is pivotal in this process. Autophagy is a highly conserved catabolic process that acts as a double-edged sword in tumorigenesis and tumor inhibition in a context-dependent manner. Depending on the stage of malignancy and cellular origin of the tumor, autophagy might result in cancer cell survival or death during the GICs' progression. Moreover, autophagy can prevent the progression of GIC in the early stages but leads to chemoresistance in advanced stages. Therefore, targeting specific arms of autophagy could be a promising strategy in the prevention of chemoresistance and treatment of GIC. It has been revealed that autophagy is a cytoplasmic event that is subject to transcriptional and epigenetic regulation inside the nucleus. The effect of epigenetic regulation (including DNA methylation, histone modification, and expression of non-coding RNAs (ncRNAs) in cellular fate is still not completely understood. Recent findings have indicated that epigenetic alterations can modify several genes and modulators, eventually leading to inhibition or promotion of autophagy in different cancer stages, and mediating chemoresistance or chemosensitivity. The current review focuses on the links between autophagy and epigenetics in GICs and discusses: 1) How autophagy and epigenetics are linked in GICs, by considering different epigenetic mechanisms; 2) how epigenetics may be involved in the alteration of cancer-related phenotypes, including cell proliferation, invasion, and migration; and 3) how epidrugs modulate autophagy in GICs to overcome chemoresistance.

Enhancing autophagy in Alzheimer's disease through drug repositioning.

Alzheimer's disease (AD) is one of the biggest human health threats due to increases in aging of the global population. Unfortunately, drugs for treating AD have been largely ineffective. Interestingly, downregulation of macroautophagy (autophagy) plays an essential role in AD pathogenesis. Therefore, targeting autophagy has drawn considerable attention as a therapeutic approach for the treatment of AD. However, developing new therapeutics is time-consuming and requires huge investments. One of the strategies currently under consideration for many diseases is "drug repositioning" or "drug repurposing". In this comprehensive review, we have provided an overview of the impact of autophagy on AD pathophysiology, reviewed the therapeutics that upregulate autophagy and are currently used in the treatment of other diseases, including cancers, and evaluated their repurposing as a possible treatment option for AD. In addition, we discussed the potential of applying nano-drug delivery to neurodegenerative diseases, such as AD, to overcome the challenge of crossing the blood brain barrier and specifically target molecules/pathways of interest with minimal side effects.

Autophagy, Unfolded Protein Response, and Neuropilin-1 Cross-Talk in SARS-CoV-2 Infection: What Can Be Learned from Other Coronaviruses.

The COVID-19 pandemic is caused by the 2019-nCoV/SARS-CoV-2 virus. This severe acute respiratory syndrome is currently a global health emergency and needs much effort to generate an urgent practical treatment to reduce COVID-19 complications and mortality in humans. Viral infection activates various cellular responses in infected cells, including cellular stress responses such as unfolded protein response (UPR) and autophagy, following the inhibition of mTOR. Both UPR and autophagy mechanisms are involved in cellular and tissue homeostasis, apoptosis, innate immunity modulation, and clearance of pathogens such as viral particles. However, during an evolutionary arms race, viruses gain the ability to subvert autophagy and UPR for their benefit. SARS-CoV-2 can enter host cells through binding to cell surface receptors, including angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1). ACE2 blockage increases autophagy through mTOR inhibition, leading to gastrointestinal complications during SARS-CoV-2 virus infection. NRP1 is also regulated by the mTOR pathway. An increased NRP1 can enhance the susceptibility of immune system dendritic cells (DCs) to SARS-CoV-2 and induce cytokine storm, which is related to high COVID-19 mortality. Therefore, signaling pathways such as mTOR, UPR, and autophagy may be potential therapeutic targets for COVID-19. Hence, extensive investigations are required to confirm these potentials. Since there is currently no specific treatment for COVID-19 infection, we sought to review and discuss the important roles of autophagy, UPR, and mTOR mechanisms in the regulation of cellular responses to coronavirus infection to help identify new antiviral modalities against SARS-CoV-2 virus.

Pleiotropic effects of statins: A focus on cancer.

The statin drugs ('statins') potently inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. Statins decrease de novo cholesterol biosynthesis and thereby reduce plasma cholesterol levels. Statins exhibit "pleiotropic" properties that are independent of their lipid-lowering effects. For example, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. Furthermore, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling. However, whether statins have clinically meaningful anti-cancer effects remains an area of active investigation. Both preclinical and clinical studies on the potential mechanisms of action of statins in several cancers have been reviewed in the literature. Considering the contradictory data on their efficacy, we present an up-to-date summary of the pleiotropic effects of statins in cancer therapy and review their impact on different malignancies. We also discuss the synergistic anti-cancer effects of statins when combined with other more conventional anti-cancer drugs to highlight areas of potential therapeutic development.

Betulin and its derivatives as novel compounds with different pharmacological effects.

Betulin (B) and Betulinic acid (BA) are natural pentacyclic lupane-structure triterpenoids which possess a wide range of pharmacological activities. Recent evidence indicates that B and BA have several properties useful for the treatment of metabolic disorders, infectious diseases, cardiovascular disorders, and neurological disorders. In the current review, we discuss B and BA structures and derivatives and then comprehensively explain their pharmacological effects in relation to various diseases. We also explain antiviral, antibacterial and anti-cancer effects of B and BA. Finally, we discuss the delivery methods, in which these compounds most effectively target different systems.

Preparation and Characterization of Simvastatin Nanocapsules: Encapsulation of Hydrophobic Drugs in Calcium Alginate.

During past few years, development of methods for physical encapsulation of drugs in biocompatible materials in mild conditions for poorly water-soluble hydrophobic drugs which are sensitive to hydrolytic conditions is of high interest in biomedical and pharmaceutical industries. The encapsulation can improve the drug solubility while decreases its side effects besides controlling its pharmacokinetic profile which results in the overall improvement of the therapeutic efficacy. In the current paper, we provide a detailed protocol for encapsulation of poorly water-soluble hydrophobic drugs which is a development of the previously developed protocol of nanocapsule formation by complex formation on the interface of emulsion droplets. The newly developed protocol is based on nanocapsule formation by complex formation on the interface of emulsion droplets except using no organic solvent for potential targeted drug delivery to glioblastoma cells. Simvastatin as a model of hydrophobic drugs of high hydrolytic sensitivity was encapsulated in calcium alginate hydrogel as a biocompatible matrix using the developed protocol. Simvastatin belongs to a group of mevalonate cascade inhibitors (statins) which have recently been considered as a possible new approach in cancer treatment especially glioblastoma. As a cholesterol biosynthesis inhibitor, it is very important to deliver statins only to target cells and not intact cells using targeted drug delivery strategies to avoid dysregulation of cholesterol biosynthesis in normal tissue. To prepare the statin drug nanocarrier's, the drug was first dissolved in polysorbate 20 nonionic surfactant solution, and then peptide modified calcium alginate was deposited on the micelles interface at neutral pH and 30 °C. The prepared nanocapsules were spherical in shape and very small in size (i.e., 17 ± 5 nm). The drug content of the nanocapsules was 117.3 mg g-1 and the drug loading efficiency for a 5-mg initial amount of the drug was 23.5% ± 3.1%.

Autophagy and cancer research in Iran.

In August 2018, three events were held in Iran on clinical biochemistry, molecular biology, cancer/autophagy, laboratory management, and proteomics. On August 25-28 at the Isfahan University of Medical Sciences, the 15th National Biochemistry Congress and the 6th International Congress on Biochemistry and Molecular Biology were held, gathering together international professors from Canada, USA, Germany, Australia, Italy, France, and Sweden, as well as Iran to discuss mainly the roles of autophagy in cancer therapy. On August 29, a one-day 'Autophagy' symposium was held at the Shiraz University of Medical Sciences. The symposium was a place for specialist talks and discussions on the double-edged role of autophagy in cancer biology, which brought together approximately 200 participants, from basic and clinical fields who are interested in the autophagy field. Furthermore, the opening ceremony for the Autophagy Research Center was held on the same day, and the establishment of the center was announced in Shiraz.

Magnetic headspace adsorptive extraction of chlorobenzenes prior to thermal desorption gas chromatography-mass spectrometry.

This study presents a new, user-friendly, cost-effective and portable headspace solid-phase extraction technique based on graphene oxide decorated with iron oxide magnetic nanoparticles as sorbent, located on one end of a small neodymium magnet. Hence, the new headspace solid-phase extraction technique has been called Magnetic Headspace Adsorptive Extraction (Mag-HSAE). In order to assess Mag-HSAE technique applicability to model analytes, some chlorobenzenes were extracted from water samples prior to gas chromatography-mass spectrometry determination. A multivariate approach was employed to optimize the experimental parameters affecting Mag-HSAE. The method was evaluated under optimized extraction conditions (i.e., sample volume, 20 mL; extraction time, 30 min; sorbent amount, 10 mg; stirring speed, 1500 rpm, and ionic strength, non-significant), obtaining a linear response from 0.5 to 100 ng L-1 for 1,3-DCB, 1,4-DCB, 1,2-DCB, 1,3,5-TCB, 1,2,4-TCB and 1,2,3-TCB; from 0.5 to 75 ng L-1 for 1,2,4,5-TeCB, and PeCB; and from 1 to 75 ng L-1 for 1,2,3,4-TeCB. The repeatability of the proposed method was evaluated at 10 ng L-1 and 50 ng L-1 spiking levels, and coefficients of variation ranged between 1.5 and 9.5% (n = 5). Limits of detection values were found between 93 and 301 pg L-1. Finally, tap, mineral and effluent water were selected as real water samples to assess method applicability. Relative recoveries varied between 86 and 110% showing negligible matrix effects.