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Overweight and obesity are major public health issues worldwide, including in Mexico, particularly among adolescents. This study aimed to analyze the associations between nutritional status and impaired executive function (EF) in Mexican adolescents. A case-control study was conducted with 98 male and female adolescents, categorized into normal weight and overweight/obese groups based on body mass index. EF was assessed using the BANFE-2 test. The prevalence of overweight and obesity was 54.3%. The EF assessment revealed that 82.45% of the overweight/obese group exhibited mild-to-severe impairment, compared to only 36.58% in the normal weight group (X2 = 21.69, p < 0.0001). In the inhibitory control assessment, adolescents with overweight and obesity performed worse than their normal-weight counterparts. Specifically, females with overweight/obesity scored lower than females with normal weight on the risk-benefit processing test. The risk of severe EF impairment significantly increased with the presence of overweight/obesity (OR = 7.8, p < 0.0001). These findings indicate that EF, particularly inhibitory control and risk-benefit processing, is impaired in adolescents with overweight or obesity.

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Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since ß-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus ß-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and ß-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of ß-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K+ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with ß-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

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Urinary tract infections are commonly caused by uropathogenic Escherichia coli (UPEC), which usually presents multiple virulence and resistance mechanisms, making it difficult to treat. It has been demonstrated that silver and polymeric nanoparticles had potential against these pathogens. In this study, we synthesized thiol chitosan-coated silver nanoparticles (SH-Cs-AgNPs) and evaluated their antibacterial, antibiofilm and antiadherence activity against clinical isolates of UPEC. The SH-Cs-AgNPs showed a spherical shape with a size of 17.80 ± 2.67 nm and zeta potential of 18 ± 2 mV. We observed a potent antibacterial and antibiofilm activity as low as 12.5 µg/mL, as well as a reduction in the adherence of UPEC to mammalian cells at concentrations of 1.06 and 0.53 µg/mL. These findings demonstrate that SH-Cs-AgNPs have potential as a new therapeutic compound against infections caused by UPEC.

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Gold nanorods (AuNRs) have attracted attention in the field of biomedicine, particularly for their potential as photothermal agents capable of killing tumor cells by photothermic ablation. In this study, the synthesis of novel AuNRs stabilized with thiolated pectin (AuNR@SH-PEC) is reported. To achieve this, thiolated pectin (SH-PEC) was obtained by chemically binding cysteamine motifs to the pectin backbone. The success of the reaction was ascertained using FTIR-ATR. Subsequently, the SH-PEC was used to coat and stabilize the surface of AuNRs (AuNR@SH-PEC). In this context, different concentrations of SH-PEC (0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mg/mL) were added to 0.50 mL of AuNRs suspended in CTAB, aiming to determine the experimental conditions under which AuNR@SH-PEC maintains stability. The results show that SH-PEC effectively replaced the CTAB adsorbed on the surface of AuNRs, enhancing the stability of AuNRs without affecting their optical properties. Additionally, scanning electron and atomic force microscopy confirmed that SH-PEC is adsorbed into the surface of the AuNRs. Importantly, the dimension size (60 × 15 nm) and the aspect ratio (4:1) remained consistent with those of AuNRs stabilized with CTAB. Then, the photothermal properties of gold nanorods were evaluated by irradiating the aqueous suspension of AuNR@SH-PEC with a CW laser (808 nm, 1 W). These results showed that photothermal conversion efficiency is similar to the photothermal conversion observed for AuNR-CTAB. Lastly, the cell viability assays confirmed that the SH-PEC coating enhanced the biocompatibility of AuNR@SH-PEC. Most important, the viability cell assays subjected to laser irradiation in the presence of AuNR@SH-PEC showed a decrease in the cell viability relative to the non-irradiated cells. These results suggest that AuNRs stabilized with thiolated pectin can potentially be exploited in the implementation of photothermal therapy.

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Pain represents one of the leading causes of suffering and disability worldwide. Currently available drugs cannot treat all types of pain and may have adverse effects. Hence, the use of pharmacological combinations is an alternative treatment strategy. Therefore, this study aimed to evaluate the combination of resveratrol and ketorolac through isobolographic analysis. CD1 mice were used to study the antinociceptive effect of this combination using the formalin test and the study was divided into two phases. In the first phase, four individual doses of each drug were evaluated, totaling eight testing groups. From these data, the median effective doses (ED50) of each drug were calculated. In the second phase, four testing groups were used to evaluate the combination of sub-doses of both drugs and obtain the experimental ED50. To evaluate gastric damage, five groups were employed, including indomethacin, vehicle, resveratrol, ketorolac, and combined resveratrol and ketorolac groups. Stomach samples from the mice were taken after 5 h of treatment, and the area of the ulcers was determined. Resveratrol plus ketorolac elicited a reduction in nociceptive behavior during both phases of the formalin test, and isobologram analysis revealed that the theoretical and experimental ED50 values of resveratrol and ketorolac did not differ significantly, implying an additive interaction between the drugs. Additionally, the drug combination did not generate gastric ulcers, thus enhancing the desired effects without increasing the adverse effects. Consequently, these findings substantiate the efficacy of the resveratrol and ketorolac combination in the formalin test, thereby highlighting its potential as a viable alternative for alleviating pain.

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Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανß3 y ανß5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.

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Pain is a complex experience that involves physical, emotional, and cognitive aspects. This review focuses specifically on the physiological processes underlying pain perception, with a particular emphasis on the various types of sensory neurons involved in transmitting pain signals to the central nervous system. Recent advances in techniques like optogenetics and chemogenetics have allowed researchers to selectively activate or inactivate specific neuronal circuits, offering a promising avenue for developing more effective pain management strategies. The article delves into the molecular targets of different types of sensory fibers such as channels, for example, TRPV1 in C-peptidergic fiber, TRPA1 in C-non-peptidergic receptors expressed differentially as MOR and DOR, and transcription factors, and their colocalization with the vesicular transporter of glutamate, which enable researchers to identify specific subtypes of neurons within the pain pathway and allows for selective transfection and expression of opsins to modulate their activity.

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Introduction: Bacterial agents and oxidative reactions are involved in health and food preservation issues, and Yucca baccata (Y. baccata) can be a source of compounds with practical applications in both areas, but its investigation remains limited. Materials and Methods: Butanolic (YBE) and aqueous (YAE) extracts were obtained from the stem of Y. baccata. The total saponin, phenolic, and flavonoid contents were analyzed in the YBE and YAE. The antioxidant capacity of the extracts was determined by the DPPH, TEAC, FRAP, and ORAC assays. Seven Gram-positive and five Gram-negative pathogenic bacteria strains were used to determine the MIC and MBC. Results: Saponin contents were 30% and 1.81% (w/w) in the YBE and YAE, respectively. The total phenolic and flavonoid contents in the extracts were 29.5 µg GAEmg-1 (2.95%) and 5.58 µg GAEmg-1 (0.56%) in the YBE and 69.92 µg QEmg-1 (7.0%) and 1.65 µg QEmg-1 (0.165%) in the YAE. The antioxidant capacity values of YBE were 29.18 µg TEmg-1, 121.8 µg TEmg-1, 33.41 µg TEmg-1, and 156.84 µg TEmg-1 by the DPPH, TEAC, FRAP, and ORAC assays, respectively. YAE had lower antioxidant values than YBE (P < 0.05). Values of 80 mgmL-1 and 100 mgmL-1 were estimated for MIC and MBC of YBE against the Gram-positive bacteria. Values of 100 mgmL-1 and 120 mgmL-1 for MIC and MBC of YBE were estimated against the Gram-negative bacteria. No MIC and MBC were obtained for YAE. Conclusion: YBE exhibited higher antioxidant activity than YAE. Apparently, antibacterial properties of the YBE tended to be higher than those of the YAE.

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Multi-drug resistant (MDR) bacteria have gained importance as a health problem worldwide, and novel antibacterial agents are needed to combat them. Silver nanoparticles (AgNPs) have been studied as a potent antimicrobial agent, capable of countering MDR bacteria; nevertheless, their conventional synthesis methods can produce cytotoxicity and environmental hazards. Biosynthesis of silver nanoparticles has emerged as an alternative to reduce the cytotoxic and environmental problems derived from their chemical synthesis, using natural products as a reducing and stabilizing agent. Sonoran Desert propolis (SP) is a poplar-type propolis rich in polyphenolic compounds with remarkable biological activities, such as being antioxidant, antiproliferative, and antimicrobial, and is a suitable candidate for synthesis of AgNPs. In this study, we synthesized AgNPs using SP methanolic extract (SP-AgNPs) and evaluated the reduction capacity of their seasonal samples and main chemical constituents. Their cytotoxicity against mammalian cell lines and antibacterial activity against multi-drug resistant bacteria were assessed. Quercetin and galangin showed the best-reduction capacity for synthesizing AgNPs, as well as the seasonal sample from winter (SPw-AgNPs). The SPw-AgNPs had a mean size of around 16.5 ± 5.3 nm, were stable in different culture media, and the presence of propolis constituents was confirmed by FT-IR and HPLC assays. The SPw-AgNPs were non-cytotoxic to ARPE-19 and HeLa cell lines and presented remarkable antibacterial and antibiofilm activity against multi-drug resistant clinical isolates, with E. coli 34 and ATCC 25922 being the most susceptible (MBC = 25 µg/mL), followed by E. coli 2, 29, 37 and PNG (MBC = 50 µg/mL), and finally E. coli 37 and S. aureus ATCC 25923 (MBC = 100 µg/mL). These results demonstrated the efficacy of SP as a reducing and stabilizing agent for synthesis of AgNPs and their capacity as an antibacterial agent.

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Petiveria alliacea L. is an herb used in traditional medicine in Mexico and its roots have been studied to treat pain. However, until now, the antinociceptive properties of the leaves have not been investigated, being the main section used empirically for the treatment of diseases. For this reason, this study aimed to evaluate the antinociceptive and toxoicological activity of various extracts (aqueous, hexanic, and methanolic) from P. alliacea L. leaves in NIH mice and to perform an in silico analysis of the phytochemical compounds. Firstly, the antinociceptive effect was analyzed using the formalin model and the different doses of each of the extracts that were administered orally to obtain the dose-response curves. In addition, acute toxicity was determined by the up and down method and serum biochemical analysis. Later, the phytochemical study of extracts was carried out by thin layer chromatography (TLC) and visible light spectroscopy, and the volatile chemical components were analyzed by gas chromatography-mass spectrometry (GC/MS). Moreover, the most abundant compounds identified in the phytochemical study were analyzed in silico to predict their biological activity (PASSonline) and toxicology (OSIRIS Property Explorer). As a result, it was known that all extracts at doses from 10 to 316 mg/kg significantly reduced the pain response in both phases of the formalin model, with values of 50-60% for the inflammatory response. The toxicological studies (DL50) exhibited that all extracts did not cause any mortality up to the 2000 mg/kg dose level. This was corroborated by the values in the normal range of the biochemical parameters in the serum. Finally, the phytochemical screening of the presence of phenolic structures (coumarins, flavonoids) and terpenes (saponins and terpenes) was verified, and the highest content was of a lipid nature, 1.65 ± 0.54 meq diosgenin/mL in the methanolic extract. A total of 54 components were identified, 11 were the most abundant, and only four (Eicosane, Methyl oleate, 4-bis(1-phenylethyl) phenol, and Ethyl linolenate) of them showed a probability towards active antinociceptive activity in silico greater than 0.5. These results showed that the P. alliacea L. leaf extract possesses molecules with antinociceptive activity.

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Sonoran propolis (SP) exerts remarkable biological activities attributed to its polyphenolic composition, mostly described as poplar-type flavonoids. It is known that polyphenols present low bioavailability derived of their molecular weight, glycosylation level, metabolic conversion, as well as interaction with the intestinal microbiota, affording limitations for possible in vivo applications. The aim of this work was to synthesize Poly-(lactide-co-glycolide) acid (PLGA) nanoparticles for encapsulation of SP, as a matrix to increase solubility of their polyphenolic compounds and improve delivery, for the evaluation of its antiproliferative activity on cancer cells. The Sonoran propolis-loaded PLGA nanoparticles (SP-PLGA NPs) were synthesized (by nanoprecipitation), and their physicochemical parameters were determined (size, morphology, zeta potential, stability, and drug release). Additionally, the antiproliferative activity of SP-PLGA nanoparticles was evaluated in vitro against murine (M12.C3.F6) and human (HeLa) cancer cell lines, including a non-cancer human cell line (ARPE-19) as control. SP-PLGA NPs presented a mean size of 152.6 ± 7.1 nm with an average negative charge of - 21.2 ± 0.7 mV. The encapsulation yield of SP into PLGA system was approximately 68.2 ± 6.0% with an in vitro release of 45% of propolis content at 48 h. SP-PLGA NPs presented antiproliferative activity against both cancer cell lines tested, with lower IC50 values in M12.C3.F6 and HeLa cell lines (7.8 ± 0.4 and 3.8 ± 0.4 µg/mL, respectively) compared to SP (24.0 ± 4.3 and 7.4 ± 0.4 µg/mL, respectively). In contrast, the IC50 of SP-PLGA NPs and SP against ARPE-19 was higher than 50 µg/mL. Cancer cells treated with SP and SP-PLGA NPs presented morphological features characteristic of apoptosis (cellular shrinkage and membrane blebs), as well as elongated cells, effect previously reported for SP, meanwhile, no morphological changes were observed with ARPE-19 cells. The obtained delivery system demonstrates appropriate encapsulation characteristics and antiproliferative activity to be used in the field of nanomedicine, therefore SP could be potentially used in antitumoral in vivo assays upon its encapsulation into PLGA nanoparticles.

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Pseudomonas aeruginosa infections have become more challenging to treat and eradicate due to their ability to form biofilms. This study aimed to produce hydrophobic nanoparticles by grafting 11-carbon and three-carbon alkyl chains to a chitosan polymer as a platform to carry and deliver carvacrol for improving its antibacterial and antibiofilm properties. Carvacrol-chitosan nanoparticles showed ζ potential values of 10.5-14.4 mV, a size of 140.3-166.6 nm, and an encapsulation efficiency of 25.1-68.8%. Hydrophobic nanoparticles reduced 46-53% of the biomass and viable cells (7-25%) within P. aeruginosa biofilms. Diffusion of nanoparticles through the bacterial biofilm showed a higher penetration of nanoparticles created with 11-carbon chain chitosan than those formulated with unmodified chitosan. The interaction of nanoparticles with a 50:50 w/w phospholipid mixture at the air-water interface was studied, and values suggested that viscoelasticity and fluidity properties were modified. The modified nanoparticles significantly reduced viable P. aeruginosa in biofilms (0.078-2.0 log CFU·cm-2) and swarming motility (40-60%). Furthermore, the formulated nanoparticles reduced the quorum sensing in Chromobacterium violaceum. This study revealed that modifying the chitosan polarity to synthesize more hydrophobic nanoparticles could be an effective treatment against P. aeruginosa biofilms to decrease its virulence and pathogenicity, mainly by increasing their ability to interact with the membrane phospholipids and penetrate preformed biofilms.

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Pharmacological treatment of pain often causes undesirable effects, so it is necessary to look for natural, safe, and effective alternatives to alleviate painful behavior. In this context, it is known that different parts of pomegranate have been widely consumed and used as preventive and therapeutic agents since ancient times. For example, it has been shown to have an antinociceptive effect, however, there are many varieties. Each part has been found to display unique and attractive pharmacological activities. The content of the active phytochemicals in pomegranate depends on the cultivar, geographical region, the maturity, and the processing method. In this context, the effects of various pomegranate varieties and other parts of the pomegranate (e.g., peel and juice) on pain behavior have not been examined. The aim was to evaluate and compare the antinociceptive effect of ethanolic extracts (PEx) and lyophilized juices (Lj) of three varieties of pomegranate in the formalin test. In addition, computer-aided analysis was performed for determining biological effects and toxicity. Peels were extracted with ethanol and evaporated by rotary evaporation, and juices were filtered and lyophilized. Wistar rats (N = 48) were randomly distributed into 8 groups (n = 6) (Vehicle, Acetylsalicylic Acid, PEx1, PEx2, PEx3, Lj1, Lj2, and Lj3). The formalin test (2%) was carried out, which consists of administering formalin in paw and counting the paw flinches for 1 h, with prior administration of treatments. All samples have an antinociceptive effect (phase 1: 2.8-10%; phase 2: 23.2-45.2%). PEx2 and Lj2 had the greatest antinociceptive effect (57.8-58.9%), and bioactive compounds such as tannins and flavonoids showed promising pharmacodynamic properties that may be involved in the antinociceptive effect, and can be considered as a natural alternative for the treatment of nociceptive and inflammatory pain.

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Bacterial infections have become one of the top ten public health concerns worldwide. These problems are aggravated with the emergence of multi-drug resistant bacterial strains. Thus, it is necessary to adopt novel technological strategies, such as development of bionanomaterials to prevent the infection, and treat this kind of bacteria. At this regard, the chemical modification of chitosan (Cs), by the covalent attachment of a hydrocarbon chain (octanoic acid), was developed to obtain hydrophobic chitosan (HCs). Then, HCs was used to synthetize nanoparticles using the well-known ionotropic gelation approach, optimizing the parameters, such as the TPP/HCs ratio and pH solution to get stable nanoparticles. Then, carvacrol (CAR) was loaded into NPs (HCs-CAR NPs) using different concentrations of 25%, 50% and 75% (%w/w CAR/HCs). The physicochemical properties for HCs-CAR NPs prepared at 50% of CAR stood out from the rest, showing a spherical morphology, with a size of 200 nm, Z potential of 10.4 mV and encapsulation efficiency of 56.28%. These formulations were chosen to evaluate the antibacterial activity, using Gram-negative (Escherichia coli) and Gram-positive bacterial model (Staphylococcus aureus). The HCs-CAR NPs showed great activity against both bacterial models, being more effective against Gram (+) strain (S. aureus), suggesting the potential application of these NPs as novel biomaterial to treat bacterial infection.

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Urinary tract infections (UTIs) belong to the most common pathologies in Mexico and are mainly caused by Uropathogenic Escherichia coli (UPEC). UPEC possesses a wide diversity of virulence factors that allow it to carry out its pathogenesis mechanism in the urinary tract (UT). The development of morphotypes in UT represents an important feature of UPEC because it is associated with complications in diagnosis of UTI. The aim of this study was to determine the presence of bacterial morphotypes, virulence genes, virulence phenotypes, antibiotic resistant, and phylogenetic groups in clinical isolates of UPEC obtained from women in Sonora, Mexico. Forty UPEC isolates were obtained, and urine morphotypes were observed in 65% of the urine samples from where E. coli was isolated. Phylogenetic group B2 was the most prevalent. The most frequent virulence genes were fimH (100%), fliCD (90%), and sfaD/focC (72%). Biofilm formation (100%) and motility (98%) were the most prevalent phenotypes. Clinical isolates showed high resistance to aminoglycosides and ß-lactams antibiotics. These data suggest that the search for morphotypes in urine sediment must be incorporated in the urinalysis procedure and also that clinical isolates of UPEC in this study can cause upper, lower, and recurrent UTI.

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Gold nanoparticles (GNPs) are an attractive nanomaterial for potential applications in therapy and diagnostics due to their capability to direct toward specific sites in the organism. However, when exposed to plasma, GNPs can interact with different biomolecules that form a dynamic nano-bio interface called a "protein corona" (PC). Remarkably, the PC could affect multiple biological processes, such as cell targeting and uptake, cytotoxicity, and nanoparticle (NP) clearance. The interaction of nanomaterials with plasmatic proteins has been widely studied under bulk conditions, however, under dynamic conditions, it has just recently been explored. Thus, to mimic a dynamic natural environment found in arteries and veins, microfluidic devices were used. In this work, gold nanorods (GNRs) were synthesized and conjugated with polyethylene glycol (PEG) to reduce their interaction with plasma proteins and increase their biocompatibility. Then, GNRs were functionalized with folic acid, a targeting ligand typically used to recognize tumor cells. The resulting nanosystem was exposed to fibrinogen (FB) to study the development and biological impact of PC formation through two strategies: bulk and laminar flow conditions. The obtained nanosystems were characterized by absorption spectrophotometry, DLS, laser Doppler microelectrophoresis, neutron activation analysis, circular dichroism spectroscopy and TEM. Finally, cell viability and cellular uptake assays were performed to study the influence of the PC on the cell viability and delivery of nanosystems.

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Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a polydimethylsiloxane (PDMS) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2), to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2 + breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties.

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Neuropathic pain is characterized by the presence of hyperalgesia and allodynia. Pharmacological treatments include the use of antiepileptics such as pregabalin or gabapentin, as well as antidepressants; however, given the role of the sigma-1 receptor in the generation and maintenance of pain, it has been suggested that sigma-1 receptor antagonists may be effective. There are also other alternatives that have been explored, such as the use of flavonoids such as quercetin. Due to the relevance of drug combinations in therapeutics, the objective of this work was to evaluate the effect of the combination of BD-1063 with quercetin in a chronic sciatic nerve constriction model using the "Surface of Synergistic Interaction" analysis method. The combination had preferable additive or synergistic effects, with BD-1063 (17.8 mg/kg) + QUER (5.6 mg/kg) showing the best antinociceptive effects. The required doses were also lower than those used individually to obtain the same level of effect. Our results provide the first evidence that the combination of a sigma-1 receptor antagonist and the flavonoid quercetin may be useful in the treatment of nociceptive behaviors associated with neuropathic pain, suggesting a new therapeutic alternative for this type of pain.

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Ovarian cancer (OC) is the deadliest gynecological cancer. Standard treatment of OC is based on cytoreductive surgery followed by chemotherapy with platinum drugs and taxanes; however, innate and acquired drug-resistance is frequently observed followed by a relapse after treatment, thus, more efficient therapeutic approaches are required. Combination therapies involving phototherapies and chemotherapy (the so-called chemophototherapy) may have enhanced efficacy against cancer, by attacking cancer cells through different mechanisms, including DNA-damage and thermally driven cell membrane and cytoskeleton damage. We have designed and synthesized poly(lactic-co-glycolic) nanoparticles (PLGA NPs) containing the chemo-drug carboplatin (CP), and the near infrared (NIR) photosensitizer indocyanine green (ICG). We have evaluated the drug release profile, the photodynamic ROS generation and photothermal capacities of the NPs. Also, the antitumoral efficiency of the NPs was evaluated using the SKOV-3 cell line as an in vitro OC model, observing an enhanced cytotoxic effect when irradiating cells with an 800 nm laser. Evidence here shown supports the potential application of the biodegradable photoresponsive NPs in the clinical stage due to the biocompatibility of the materials used, the spatiotemporal control of the therapy and, also, the less likely development of resistance against the combinatorial therapy.

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INTRODUCTION: Gold nanorods are highly reactive, have a large surface-to-volume ratio, and can be functionalized with biomolecules. Gold nanorods can absorb infrared electromagnetic radiation, which is subsequently dispersed as local heat. Gold nanoparticles can be used as powerful tools for the diagnosis and therapy of different diseases. To improve the biological barrier permeation of nanoparticles with low cytotoxicity, in this study, we conjugated gold nanorods with cell-penetrating peptides (oligoarginines) and with the amphipathic peptide CLPFFD. METHODS: We studied the interaction of the functionalized gold nanorods with biological membrane models (liposomes) by dynamic light scattering, transmission electron microscopy and the Langmuir balance. Furthermore, we evaluated the effects on cell viability and permeability with an MTS assay and TEM. RESULTS AND DISCUSSION: The interaction study by DLS, the Langmuir balance and cryo-TEM support that GNR-Arg7CLPFFD enhances the interactions between GNRs and biological membranes. In addition, cells treated with GNR-Arg7CLPFFD internalized 80% more nanoparticles than cells treated with GNR alone and did not induce cell damage. CONCLUSION: Our results indicate that incorporation of an amphipathic sequence into oligoarginines for the functionalization of gold nanorods enhances biological membrane nanoparticle interactions and nanoparticle cell permeability with respect to nanorods functionalized with oligoarginine. Overall, functionalized gold nanorods with amphipathic arginine rich peptides might be candidates for improving drug delivery by facilitating biological barrier permeation.

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