Wireless wearable potentiometric sensor for simultaneous determination of pH, sodium and potassium in human sweat.

This paper reports on the development of a flexible-wearable potentiometric sensor for real-time monitoring of sodium ion (Na+), potassium ion (K+), and pH in human sweat. Na0.44MnO2, polyaniline, and K2Co[Fe(CN)6] were used as sensing materials for Na+, H+ and K+ monitoring, respectively. The simultaneous potentiometric Na+, K+, and pH sensing were carried out by the developed sensor, which enables signal collection and transmission in real-time to the smartphone via a Wi-Fi access point. Then, the potentiometric responses were evaluated by a designed android application. Na+, K+, and pH sensors illustrated high sensitivity (59.7 ± 0.8 mV/decade for Na+, 57.8 ± 0.9 mV/decade for K+, and 54.7 ± 0.6 mV/pH for pH), excellent stability, and good batch-to-batch reproducibility. The results of on-body experiments demonstrated that the proposed platform is capable of real-time monitoring of the investigated ions.

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.

A paired emitter-detector diode-based photometer for the determination of sodium hypochlorite adulteration in milk.

This paper reports on developing a low cost but efficient paired emitter-detector diode (PEDD)-based photometer. The photometer consists of a white light-emitting diode (LED) as the emitter diode, an RGB LED as the detector diode, and a multimeter for recoding the signal. The developed PEDD-based photometer was utilized for the determination of liquid bleach adulteration in cow milk samples. N,N-Diethyl-p-phenylenediamine sulfate aqueous solution of pH 6 was used as a probe to monitor the presence of residual active chlorine in milk. The results showed that the developed method could be used to determine sodium hypochlorite in the concentration range of 0.5 to 20.0 ppm Cl2 with 0.14 and 0.46 ppm Cl2 limit of detection and limit of quantification, respectively. The intraday and interday precisions of the method at two concentration levels of 5.5 and 13.7 ppm Cl2 were 1.04% and 0.52%, and 1.81% and 1.02%, respectively. The recoveries of 114.2% and 106.9% were obtained for 5.5 and 13.7 ppm Cl2 concentrations levels, respectively. Real sample analyzes results showed that "maybe" liquid bleach adulteration in milk is the case for local distributors of raw milk.

Biodegradable and Non-Biodegradable Biomaterials and Their Effect on Cell Differentiation.

Biomaterials for tissue scaffolds are key components in modern tissue engineering and regenerative medicine. Targeted reconstructive therapies require a proper choice of biomaterial and an adequate choice of cells to be seeded on it. The introduction of stem cells, and the transdifferentiation procedures, into regenerative medicine opened a new era and created new challenges for modern biomaterials. They must not only fulfill the mechanical functions of a scaffold for implanted cells and represent the expected mechanical strength of the artificial tissue, but furthermore, they should also assure their survival and, if possible, affect their desired way of differentiation. This paper aims to review how modern biomaterials, including synthetic (i.e., polylactic acid, polyurethane, polyvinyl alcohol, polyethylene terephthalate, ceramics) and natural (i.e., silk fibroin, decellularized scaffolds), both non-biodegradable and biodegradable, could influence (tissue) stem cells fate, regulate and direct their differentiation into desired target somatic cells.

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.

Wearable Potentiometric Sensor Based on Na0.44MnO2 for Non-invasive Monitoring of Sodium Ions in Sweat.

Here, we present a wearable potentiometric ion sensor for real-time monitoring of sodium ions (Na+) in human sweat samples using Na0.44MnO2 as the sensing material. Na0.44MnO2 is an attractive material for developing wearable electrochemical sensors due to its good Na+ incorporation ability, electrical conductivity, stability, and low fabrication cost. In the first step, the analytical performance of the electrode prepared using Na0.44MnO2 is presented. Then, a miniaturized potentiometric cell integrated into a wearable substrate is developed, which reveals a Nernstian response (58 mV dec-1). We achieved the detection of Na+ in the linear ranges of 0.21-24.54 mmol L-1, which is well within the physiological range of Na+. Finally, for on-body sweat analysis, the potentiometric sensor is fully integrated into a headband textile. This platform can be employed for non-invasive analysis of Na+ in human sweat for healthcare and disease diagnosis.

Emerging Advances of Nanotechnology in Drug and Vaccine Delivery against Viral Associated Respiratory Infectious Diseases (VARID).

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.

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.

Self-assembled graphene-based microfibers with eclectic optical properties.

The construction of graphene-based microfibers with reinforced mechanical and electrical properties has been the subject of numerous researches in recent years. However, the fabrication of graphene-based fibers with remarkable optical features still remains a challenge and has not been addressed so far. This paper aims to report a series of flexible self-assembled fibers, synthesized through a few-minute sonication of thermally oxidized graphene oxide nanosheets, so-called Nanoporous Over-Oxidized Graphene (NOG), in an acidic medium. These free-standing glassy fibers were classified into four distinct morphological structures and displayed a collection of intriguing optical properties comprising high transparency, strong birefringence, fixed body colorations (e.g. colorless, blue, green, and red), tunable interference marginal colorations, UV-visible-near IR fluorescence, and upconversion emissions. Moreover, they exhibited high chemical stability in strongly acidic, basic, and oxidizing media. The foregoing notable attributes introduce the NOG fiber as a promising candidate both for the construction of graphene-based photoluminescent textiles and the development of a wide variety of optical applications.

Application of magnetic nanomaterials in electroanalytical methods: A review.

Magnetic nanomaterials (MNMs) have gained high attention in different fields of studies due to their ferromagnetic/superparamagnetic properties and their low toxicity and high biocompatibility. MNMs contain magnetic elements such as iron and nickel in metallic, bimetallic, metal oxide, and mixed metal oxide. In electroanalytical methods, MNMs have been applied as sorbents for sample preparation before the electrochemical detection (sorbent role), as the electrode modifier (catalytic role), and the integration of the above two roles (as both sorbent and catalytic agent). In this paper, the application of MNMs in electroanalytical methods have been classified based on the main role of the nanomaterial and discussed separately. Furthermore, catalytic activities of MNMs in electroanalytical methods such as redox electrocatalytic, nanozymes catalytic (peroxidase, catalase activity, oxidase activity, superoxide dismutase activity), catalyst gate, and nanocontainer have been discussed.

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. RESULTS: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61-2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07-2.33), P = 0.312]. CONCLUSIONS: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

Ultrasound-assisted dispersive liquid antisolvent precipitation for extraction of polar organic compounds in water.

This paper reports on the development of an extraction method called "ultrasound-assisted dispersive liquid antisolvent precipitation (UA-DLAP)". The developed method is a combination of dispersive liquid-liquid microextraction (DLLME) and liquid antisolvent precipitation (LAP) methods. Unlike DLLME, the extraction solvent in UA-DLAP is replaced with a bad solvent for the analyte which has a low affinity toward the analyte (antisolvent). Unlike LAP, in UA-DLAP the analyte is dissolved in water, the antisolvent is water-immiscible and denser than water, and the needed volume of the antisolvent is in microliter range. In UA-DLAP, after the addition of a mixture of the antisolvent and a disperser solvent to the sample solution under sonication, a cloudy mixture containing the antisolvent micro/nanodroplets appears. After centrifugation of the mixture, three phases appear (a water-rich phase in the top, an analyte rich precipitate phase in middle, and an antisolvent rich phase in the bottom). Finally, the analyte rich precipitate phase is separated and dissolved in a back-extraction solvent. To evaluate the efficiency of the UA-DLAP method and its possible mechanism of action, three model polar organic compounds in water were extracted by UA-DLAP and determined spectrophotometrically. The results showed that the precipitate phase for all of the investigated analytes was nanostructured. The limits of detection were 22 ng mL-1, 11 ng mL-1, and 3.9 ng mL-1 for doxorubicin, methylene blue, and Congo red, respectively. Respective experimental enrichment factors were 18.3, 27.8, and 31.1.

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.

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%.

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.