Hyaluronic Acid-Targeted Niosomes for Effective Breast Cancer Chemostarvation Therapy.

Chemotherapy is widely used for cancer therapy; however, its efficacy is limited due to poor targeting specificity and severe side effects. Currently, the next generations of delivery systems with multitasking potential have attracted significant attention for cancer therapy. This study reports on the design and synthesis of a multifunctional nanoplatform based on niosomes (NIO) coloaded with paclitaxel (PTX), a chemotherapeutic drug commonly used to treat breast cancer, and sodium oxamate (SO), a glycolytic inhibitor to enhance the cytotoxicity of anticancer drug, along with quantum dots (QD) as bioimaging agents, and hyaluronic acid (HA) coating for active targeting. HN@QPS nanoparticles with a size of ∼150 nm and a surface charge of -39.9 mV with more than 90% EE for PTX were synthesized. Codelivery of SO with PTX remarkably boosted the anticancer effects of PTX, achieving IC50 values of 1-5 and >0.5 ppm for HN@QP and HN@QPS, respectively. Further, HN@QPS treatment enhanced the apoptosis rate by more than 70% in MCF-7 breast cancer cells without significant cytotoxicity on HHF-2 normal cells. Also, quantification of mitochondrial fluorescence showed efficient toxicity against MCF-7 cells. Moreover, the cellular uptake evaluation demonstrated an improved uptake of HN@Q in MCF-7 cells. Taken together, this preliminary research indicated the potential of HN@QPS as an efficient targeted-dual drug delivery nanotheranostic against breast cancer cells.

Impact of grinding balls on the size reduction of Aprepitant in wet ball milling procedure.

One of the widely used approaches for improving the dissolution of poorly water-soluble drugs is particle size reduction. Ball milling is a mechanical, top-down technique used to reduce particle size. The effect of ball number, ball size, and milling speed on the properties of milled Aprepitant is evaluated. A full factorial design was employed to investigate the influence of affecting factors on particle size reduction. The initial suspension was made by suspending the drug in distilled water using excipients followed by milling in a planetary ball mill. Ball size, ball number, and milling speed modulated particle size distribution of Aprepitant. Increasing the number of balls from minimum to maximum for each ball size led to approximately a 28% reduction in mean particle size, a 37% decrease in D90%, and a 25% decrease in the ratio of volume mean particle diameter to numeric mean particle diameter. On average, using 10 mm balls instead of 30 mm balls reduced mean particle size by 1.689 µm. As a result, ball size, ball number, and milling speed are three effective factors in the process of ball milling. By increasing the ball number and decreasing the ball size, efficient micronization of drug particles takes place and the particle size is more uniform.

Incorporating mesoporous SiO2-HA particles into chitosan/hydroxyapatite scaffolds: A comprehensive evaluation of bioactivity and biocompatibility.

In this work, composite scaffolds with various composition ratios of chitosan (CS), hydroxyapatite (HA), and mesoporous SiO2 particles co-synthesized with hydroxyapatite (SiO2-HA) were fabricated via the freeze-drying method for bone tissue engineering applications. Morphological studies showed that adding mesoporous particles resulted in a structure with a more uniformly porous geometry, subsequently leading to reduced biodegradation rates and water absorption in the scaffolds. The bioactivity results showed the introduction of mesoporous particles notably enhanced the coverage of the scaffold surface with apatite films. Moreover, biocompatibility assessments using sarcoma osteogenic cell line (SAOS-2) highlighted mesoporous particles' positive impact on cell adhesion and growth. The fluorescence images showed spindle-shaped cells with a greater number and normal cell nuclei for the scaffolds containing mesoporous SiO2-HA particles. The MTT cytotoxicity results indicated that the scaffolds containing mesoporous particles showed approximately 25 % higher cell survival more than single chitosan-based ones. What is more, the mesoporous-containing scaffolds occurred to have the best alkaline phosphatase test (ALP) activity among all scaffolds. It is important to add that CS/HA/mesoporous SiO2-HA scaffolds including SAOS-2 cells showed no sign of either early or late apoptosis. These findings affirm the potential of CS/HA/mesoporous SiO2-HA scaffolds as promising implants for bone tissue engineering.

Designing and fabrication of colloidal nano-phytosomes with gamma-oryzanol and phosphatidylcholine for encapsulation and delivery of polyphenol-rich extract from pomegranate peel.

Nano-carriers are well-known delivery systems to encapsulate different bioactive compounds and extracts. Such nano-systems are used in various food and drug areas to protect active ingredients, increase bioavailability, control the release, and deliver bioactive substances. This study aimed to design and fabricate a stable colloidal nano-delivery system to better preserve the antioxidant properties of pomegranate peel extract (PPE) and protect its sustained release in a gastrointestinal model. To achieve this goal, a nano-phytosomal system was fabricated with plant-based, cost-effective, and food-grade compounds, i.e., phosphatidylcholine (PC) and gamma-oryzanol (GO) for encapsulation of PPE. To fabricate the nano-phytosomes, thin film hydration/sonication method was used. The parameters of particle size, zeta potential, polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) were investigated to evaluate the efficiency of the produced nano-system. In summary, the size, zeta potential, PDI, LC, and EE of homogenous spherical PC-GO-PPE nano-phytosomes (NPs) in the ratio of 8:2:2 % w/w were achieved as 60.61 ± 0.81 nm, -32.24 ± 0.84 mV, 0.19 ± 0.01, 19.13 ± 0.30 %, and 95.66 ± 1.52 %, respectively. Also, the structure of NPs was approved by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). The optimized NPs were stable during one month of storage at 4 °C, and changes in the size of particles and PPE retention rate were insignificant (p > 0.05). The nano-encapsulation of PPE significantly decreased the loss of its antioxidant activity during one month of storage at 4 °C. The optimized NPs exhibited prolonged and sustained release of PPE in a gastrointestinal model, so that after 2 h in simulated gastric fluid (SGF) and 4 h in simulated intestinal fluid (SIF), 22.66 ± 2.51 % and 69.33 ± 4.50 % of initially loaded PPE was released, respectively. Optimized NPs had considerable cytotoxicity against the Michigan Cancer Foundation-7 cell line (MCF7) (IC50 = 103 µg/ml), but not against Human Foreskin Fibroblast cell line (HFF-2) (IC50 = 453 µg/ml). In conclusion, spherical PC-GO-PPE NPs were identified as a promising delivery system to efficiently encapsulate PPE, as well as protect and preserve its bioactivity, including antioxidant and cytotoxicity against cancer cell line.

Pinuseldarone, a Clerodane-Type Diterpene from Pinus eldarica Needles and Phytochemicals as Novel Agents for Regulating Brown Adipogenesis and Thermogenesis.

Phytochemical investigation of the MeOH extract of Pinus eldarica needles led to the isolation and identification of a new clerodane-type diterpene, pinuseldarone (1), along with a known flavonoid, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2), through HPLC purification. The structure of the new compound 1 was elucidated using spectroscopic methods, including 1D and 2D NMR, as well as HRESIMS. Its absolute configuration was established through NOESY analysis and computational methods, including electronic circular dichroism (ECD) calculations and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ probability analysis. The metabolic implications of the isolated compounds were assessed using a cultured brown adipocyte model derived from murine brown adipose tissue. It was observed that treatment with dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2) downregulates the adipogenic marker C/EBPδ and fatty acid transporter CD36, resulting in a significant reduction in lipid accumulation during brown adipocyte differentiation. However, pinuseldarone (1) treatment did not affect brown adipocyte differentiation. Interestingly, pretreatment with pinuseldarone (1) potentiated the pharmacological stimulation of brown adipocytes, seemingly achieved by sensitizing their response to ß3-adrenoreceptor signaling. Therefore, our findings indicate that phytochemicals derived from P. eldarica needles could potentially serve as valuable compounds for adjusting the metabolic activity of brown adipose tissue, a vital component in maintaining whole-body metabolic homeostasis.

White-brown adipose tissue interplay in polycystic ovary syndrome: Therapeutic avenues.

This study highlights the therapeutic potential of activating brown adipose tissue (BAT) for managing polycystic ovary syndrome (PCOS), a prevalent endocrine disorder associated with metabolic and reproductive abnormalities. BAT plays a crucial role in regulating energy expenditure and systemic insulin sensitivity, making it an attractive target for the treatment of obesity and metabolic diseases. Recent research suggests that impaired BAT function and mass may contribute to the link between metabolic disturbances and reproductive issues in PCOS. Additionally, abnormal white adipose tissue (WAT) can exacerbate these conditions by releasing adipokines and nonesterified fatty acids. In this review, we explored the impact of WAT changes on BAT function in PCOS and discussed the potential of BAT activation as a therapeutic strategy to improve PCOS symptoms. We propose that BAT activation holds promise for managing PCOS; however, further research is needed to confirm its efficacy and to develop clinically feasible methods for BAT activation.

The effect of nanoparticle coating on biological, chemical and biophysical parameters influencing radiosensitization in nanoparticle-aided radiation therapy.

Nanoparticle-based composites have the potential to meet requirements for radiosensitization in both therapeutic and diagnostic applications. The radiosensitizing properties of nanoparticles could be reliant on the nature of their coating layer. Any gains in reduced toxicity and aggregation or improved delivery to tumor cells for coated nanoparticles must be weighed against the loss of dose enhancement. The radiosensitization potential of coated NPs is confirmed by numerous studies but in most of them, the coating layer is mostly applied to reduce toxicity of the NPs and for stability and biocompatibility aims. While the direct effects of the coating layer in radiosensitization-were ignored and not considered. This review provides an overview of double-edged impact of nanoparticle coating on the radiosensitization potential of nanostructures and discusses the challenges in choosing appropriate coating material in the aim of achieving improved radioenhancement. Coating layer could affect the radiosensitization processes and thereby the biological outcomes of nanoparticle-based radiation therapy. The physicochemical properties of the coating layer can be altered by the type of the coating material and its thickness. Under low-energy photon irradiation, the coating layer could act as a shield for nanoparticles capable of absorb produced low-energy electrons which are important levers for local and nanoscopic dose enhancement. Also, it seems that the coating layer could mostly affect the chemical process of ROS production rather than the physicochemical process. Based on the reviewed literature, for the irradiated coated nanoparticles, the cell survival and viability of cancer cells are decreased more than normal cells. Also, cell cycle arrest, inhibition of cell proliferation, DNA damage, cell death and apoptosis were shown to be affected by coated metallic nanoparticles under irradiation.

Ruthenium (II) Complexes Based on Phenanthroline-Tetrazole as Possible Anticancer Agents.

Background: The development of platinum-based metal complexes in oncology is limited due to vigorous toxicity and drug resistance. Objectives: This work aimed to study the cytotoxic activity and apoptosis induction of ruthenium complexes in a B16F10 cell line therapy. Methods: We prepared a series of innovative Ru(II) complexes [Ru(Tzphen)(bpy)(dcbpy)]+2 (S1), [Ru(dcbpy)2(Tzphen)]+2 (S2), [Ru(Phen)2(Tzphen)]+2 (S3), [Ru(Tzphen)(bpy)2]+2 (S4), [Ru(dmbpy)2(Tzphen)]+2 (S5) based on 1,10-phenanthroline ligand containing tetrazole and their anticancer properties investigated by cytotoxicity in vitro, reactive oxygen species, apoptosis with annexin V/PI staining method, autophagy, and cell uptake. Results: S1, S2, S3, S4, and S5 complexes showed comparable cytotoxicity activity relative to cisplatin against the B16F10 model. Moreover, intracellular ROS levels increased due to the presence of the complexes. Among the investigated complexes, the cells treated with the S5 complex indicated the highest apoptotic percentage (Q3) of 14.9% compared to the controls. The cell adsorption of the complexes also showed that the S4 and S5 complexes had higher cell adsorption, better internalization, and higher fluorescence light intensity. Conclusions: The present work provides important guidance for designing and using Ru complexes in cancer therapy.

Comparison of global decolonization efficacy with mupirocin nasal drop and chlorhexidine mouthwash in acute leukemia patients: randomized clinical trial.

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).

In situ produced exopolysaccharides by Bacillus coagulansIBRC-M 10807 and its effects on properties of whole wheat sourdough.

This study aimed to investigate in situ exopolysaccharides (EPSs) production by Bacillus coagulans IBRC-M 10807 under different fermentation conditions to improve the technical-functional properties of whole wheat flour sourdough and obtain high-quality products. For this purpose, the effectiveness of four efficient factors including B. coagulans (8 Log CFU/g), FOS (0%, 2.5%, and 5% based on flour weight), fermentation temperature (30, 35, and 40°C), and fermentation time (12, 18, and 24 h) was investigated on the production of functional sourdough. Our work focused on optimizing probiotic sourdough by investigating probiotic viability, pH, total titratable acidity, antioxidant properties, and EPS measurement. The first optimal formulation for maximized production of the in situ EPSs by the numerical optimization included FOS 0%, B. coagulans IBRC-M 10807 8 Log CFU/g, fermentation temperature of 30°C, and fermentation time of 12 h. In this case, EPSs was 59.28 mg/g and probiotic was 10.99 Log CFU/g. The second optimal formula by considering the highest viability of probiotic together with EPS production was determined as FOS 4.71%, B. coagulans IBRC-M 10807, 8 Log CFU/g, fermentation temperature of 30°C, and fermentation time of 20 h. The predicted amount of the EPSs and probiotic viability via the second formulation were 54.4 mg/g and 11.18 Log CFU/g, respectively. Analyses of optimal sourdough using FTIR, SEM, and DSC revealed that FOS and probiotics significantly reduced the enthalpy of amylopectin retrogradation and delayed it compared to other samples. Therefore, improving the final product's technological capabilities and shelf life can be credited with potential benefits.

Ultrasonication/dynamic maceration-assisted extraction method as a novel combined approach for recovery of phenolic compounds from pomegranate peel.

According to recent studies, pomegranate peel (PP) has the potential to be inverted from environmental pollutant waste to wealth due to possessing valuable phenolic compounds at a higher amount compared to edible parts. So far, different types of biological activities such as antimutagenic, antiproliferative, anti-inflammatory, and chemo-preventive properties were stated for pomegranate peel extract (PPE) according to chemical composition. In the present research, the probable intensifying effects of two extraction methods and optimum conditions for novel combined method of ultrasonication and dynamic maceration-assisted extraction of PPE using response surface methodology (RSM) were determined. A Box-Behnken Design (BBD) was employed to optimize three extraction variables, including sonication time (X1), sonication temperature (X2), and stirring speed (X3) for the achievement of high extraction yield of the phenolic compounds and antioxidant activity. The optimized conditions to obtain maximum extraction efficiency were determined as X1 = 70 min, X2 = 61.8°C, and X3 = 1000 rpm. The experimental values were in line with the values anticipated by RSM models, which indicates the appropriateness of the applied quadratic model and the accomplishment of RSM in optimizing the extraction conditions. The results suggest that the extraction of PPE by mix of ultrasonication as a modern method and dynamic maceration as a conventional method could improve its bioactive extractability and the obtained values were higher than any of the methods used. In other words, these two methods together have intensifying effects in increasing extraction efficiency which could further be utilized in food and agricultural industry.

Non-viral and viral delivery systems for hemophilia A therapy: recent development and prospects.

Recent advancements have focused on enhancing factor VIII half-life and refining its delivery methods, despite the well-established knowledge that factor VIII deficiency is the main clotting protein lacking in hemophilia. Consequently, both viral and non-viral delivery systems play a crucial role in enhancing the quality of life for hemophilia patients. The utilization of viral vectors and the manipulation of non-viral vectors through targeted delivery are significant advancements in the field of cellular and molecular therapies for hemophilia. These developments contribute to the progression of treatment strategies and hold great promise for improving the overall well-being of individuals with hemophilia. This review study comprehensively explores the application of viral and non-viral vectors in cellular (specifically T cell) and molecular therapy approaches, such as RNA, monoclonal antibody (mAb), and CRISPR therapeutics, with the aim of addressing the challenges in hemophilia treatment. By examining these innovative strategies, the study aims to shed light on potential solutions to enhance the efficacy and outcomes of hemophilia therapy.

Targeted Delivery of Pennyroyal via Methotrexate Functionalized PEGylated Nanostructured Lipid Carriers into Breast Cancer Cells; A Multiple Pathways Apoptosis Activator.

Purpose: Pennyroyal is a species of the Lamiaceae family with potent anti-cancer and antioxidant properties. Combining this antioxidant with chemotherapeutic agents enhances the effectiveness of these agents by inducing more apoptosis in cancerous cells. Methods: Here, methotrexate (MTX) combined with pennyroyal oil based on PEGylated nanostructured lipid carriers (NLCs) was assessed. These nanoparticles were physiochemically characterized, and their anti-cancer effects and targeting efficiency were investigated on the folate receptor-positive human breast cancer cell line (MCF-7) and negative human alveolar basal epithelial cells (A549). Results: Results showed a mean size of 97.4 ± 12.1 nm for non-targeted PEGylated NLCs and 220.4 ± 11.4 nm for targeted PEGylated NLCs, with an almost small size distribution assessed by TEM imaging. Furthermore, in vitro molecular anti-cancer activity investigations showed that pennyroyal-NLCs and pennyroyal-NLCs/MTX activate the apoptosis and autophagy pathway by changing their related mRNA expression levels. Furthermore, in vitro cellular studies showed that these changes in the level of gene expression could lead to a rise in apoptosis rate from 15.6 ± 8.1 to 25.0 ± 3.2 (P<0.05) for the MCF-7 cells treated with pennyroyal-NLCs and pennyroyal-NLCs/MTX, respectively. Autophagy and reactive oxygen species (ROS) cellular evaluation indicated that treating the cells with pennyroyal-NLCs and pennyroyal-NLCs/MTX could significantly increase their intensity in these cells. Conclusion: Our results present a new NLCs-based approach to enhance the delivery of pennyroyal and MTX to cancerous breast tissues.

Polycarbonate-coated magnetic nanoparticles for the extraction of imipramine and its primary metabolite from urine.

This study introduces a reliable and inexpensive magnetic dispersive solid phase extraction to extract imipramine and its primary metabolite (desipramine) from urine samples. To accomplish this aim, Fe3 O4 magnetic nanoparticles were synthesized by sonication, subsequently, polycarbonate was precipitated gradually onto the surface of them to form the adsorbent. Extraction recoveries of 85% and 76%, enrichment factors of 57 and 51, limits of detection of 2.5 and 2.8 µg/L, and limits of quantification of 8.3 and 9.3 µg/L were obtained for imipramine and desipramine under the optimal conditions, respectively. In addition, relative standard deviations for intra- (n = 6) and inter-day (n = 5) precisions at two concentrations (50 and 100 µg/L of each analyte) were less than or equal to 4%. Short extraction time, good repeatability, high enrichment factors, and simplicity are the main advantages of the proposed method.

Carboxymethyl chitosan-gelatin-mesoporous silica nanoparticles containing Myrtus communis L. extract as a novel transparent film wound dressing.

Wound healing and health care requirements have attracted more attention, and the need to develop new drug-containing dressings to accelerate wound healing is required. Carboxymethyl chitosan (CMCS)/gelatin-based films with mesoporous silica nanoparticles (MSNs) containing the Myrtus communis L. (Myrtle) aqueous extract were designed to answer this demand. Myrtle aqueous extract included total phenolic content and good free radical scavenging ability in vitro assay. The infrared spectroscopy characterized the functional groups of myrtle extract and biocomposite films. It was found that mesoporous silica nanoparticles increased the tensile strength of the flexible dressings, which is essential in therapeutic uses. MSNs influenced swelling ratio, oxygen, and water vapor permeability that indicates the CMCS/Gelatin/Myrtle/5 % MSNs wound dressing can absorb wound exudates and preserve skin moisture. Also, these biocompatible nanoparticles reduced the cytotoxicity of fibroblast cells due to the decelerated drug release. Correspondingly, silica nanoparticles affected the extract release rate and could accumulate and release the extract prolonged in CMCS/Gelatin/Myrtle/5 % MSNs models. Finally, histological analysis showed collagen growth and fibroblast migration in wounds treated with CMCS/Gelatin/Myrtle/5 % MSNs, causing proper wound contraction and accelerating wound healing in mice models. The results suggest that CMCS/Gelatin/Myrtle/5 % MSNs films have a beneficial application as wound dressings.

Increased antibiofilm and growth inhibitory effect of Imipenem/Cilastatin nanoliposomes against clinical Pseudomonas aeruginosa isolates.

Numerous infections are linked to Pseudomonas aeruginosa. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-Pseudomonas aeruginosa effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates' pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm-1 and 1650 cm-1, demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics.

The profile of key gut microbiota members and short-chain fatty acids in patients with sepsis.

Sepsis is a complex clinical disorder with heterogeneous etiological factors. Given its high mortality rate, it is considered a global health issue. Recently, the link between gut microbiota and their metabolites, especially short-chain fatty acids, in the pathophysiology of sepsis has been reported. However, there are few findings to confirm this relationship. This study aimed to evaluate some key gut microbiota members, pathogenic bacteria, and short-chain fatty acids in non-ICU patients with sepsis caused by bacteremia compared to a control group. In this case-control study, 45 stool samples from patients with sepsis and 15 healthy persons were collected from October 2021 to August 2022 in Tabriz, Iran. The position of some gut microbiota members and the main short-chain fatty acids concentration were assessed in the two groups by the Q-PCR and the high-performance liquid chromatography system. Faecalibacterium prausnitzii and Bifidobacterium sp. As bacterial with protective features in non-ICU patients with sepsis decreased significantly. Moreover, the concentrations of acetic acid and propionic acid significantly decreased in this group compared to the healthy volunteers. In contrast, the pathogenic bacteria members such as Enterobacteriaceae and Bacteroides sp. Increased significantly in the patients compared to the healthy individuals. The concentration of butyric acid decreased in the patients, but this change was not significant in the two groups. Protective and immune functions of F. prausnitzii and Bifidobacterium sp., as well as acetate and propionate, are evident. In this investigation, this profile was significantly reduced in non-ICU patients with sepsis compared to the control group.

Short-chain fatty acids profile in patients with SARS-CoV-2: A case-control study.

Background and Aims: SARS-CoV-2, as a new pandemic disease, affected the world. Short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids are the main metabolites of human gut microbiota. The positive effects of SCFAs have been shown in infections caused by respiratory syncytial virus, adenovirus, influenza, and rhinovirus. Therefore, this study aimed to evaluate the concentration of SCFAs in patients with SARS-CoV-2 compared with the healthy group. Methods: This research was designed based on a case and control study. Twenty healthy individuals as the control group and 20 persons admitted to the hospital with a positive test of coronavirus disease (COVID-19) real-time polymerase chain reaction were included in the study as the patient group from September 2021 to October 2021, in Tabriz, Iran. Stool specimens were collected from volunteers, and analysis of SCFAs was carried out by a high-performance liquid chromatography system. Results: The amount of acetic acid in the healthy group was 67.88 ± 23.09 µmol/g, while in the group of patients with COVID-19 was 37.04 ± 13.29 µmol/g. Therefore, the concentration of acetic acid in the patient group was significantly (p < 0.001) lower than in the healthy group. Propionic and butyric acid were present in a higher amount in the control group compared with the case group; however, this value was not statistically significant (p > 0.05). Conclusion: This study showed that the concentration of acetic acid as the metabolite caused by gut microbiota is significantly disturbed in patients with COVID-19. Therefore, therapeutic interventions based on gut microbiota metabolites in future research may be effective against COVID-19.

Nano-invasomes for simultaneous topical delivery of buprenorphine and bupivacaine for dermal analgesia.

Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid-based nanovesicles for the co-delivery of buprenorphine and bupivacaine to efficiently target skin-concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in-vitro drug release of vesicles were characterized. Ex-vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full-thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex-vivo fluorescent dye tracking. Estimation of in-vivo pain responses by the tail-flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug-free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10 min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex-vivo and in-vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting.