Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.

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.

Hydrophobic Chitosan Nanoparticles Loaded with Carvacrol against Pseudomonas aeruginosa Biofilms.

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.

Sigma-1 receptor antagonist (BD-1063) potentiates the antinociceptive effect of quercetin in neuropathic pain induced by chronic constriction injury.

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.

Poly(lactic-co-glycolic acid) nanoparticles for sustained release of allyl isothiocyanate: characterization, in vitro release and biological activity.

The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24 h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.

Beneficial effects of lipidic extracts of saladette tomato pomace and Serenoa repens on prostate and bladder health in obese male Wistar rats.

BACKGROUND: Obesity is associated with increased risk of a number of serious medical conditions, including urological disorders. This study investigated the effect of lipidic extracts of saladette tomato pomace (STP) and Serenoa repens (SR) on the prostate and bladder in a rat obese model induced by high-carbohydrate diet. RESULTS: High-sucrose-fed rats showed higher prostate weight as well as increased contractility and stromal and epithelial hyperplasia in the prostate. Treatment with STP and SR improved contractility and diminished hyperplasia and hypertrophy in the prostate. Obese animals also showed impaired bladder contractility, but neither extract reversed this deterioration. In the histological study, a disarray in the process of smooth muscle cell proliferation with non-parallel fibers was observed; interestingly, treatment with STP and SR led to improvement in this derangement. CONCLUSION: These findings indicated impaired contractility and hyperplasia in the prostate and bladder of obese rats induced by high sucrose. STP and SR could enhance prostate function by reducing contractility and hyperplasia and improve smooth muscle fiber structure and decrease cell proliferation in the bladder, suggesting their possible health-beneficial effects on lower urinary tract symptoms. © 2017 Society of Chemical Industry.

Nociceptive Alteration by High Sucrose Diet in Hypoestrogenic Wistar Rats.

Preclinical Research Obesity is a risk factor associated with alterations in pain perception. The aim of this study was to analyse a time-course of nociceptive responses (plantar test) in hypoestrogenic rats after the induction of obesity. Animals (hypoestrogenic and naïve) received either a hypercaloric or regular diet for 24 weeks. Thermal nociception and body weight were measured during this period. At the 4th and 17th weeks after treatment, oral glucose tolerance, blood insulin levels, abdominal fat weight, and uric acid levels were measured. The hypoestrogenic rats on a high sucrose diet had higher body weight and abdominal fat weight than control rats. A biphasic response was observed in the ovariectomized group fed with sucrose with thermal latency being decreased in the fourth week. During weeks 12-18, thermal latency increased compared to that of the hypoestrogenic control. There were no differences in basal blood glucose levels at the 4th and 17th weeks; however, oral glucose tolerance, insulin, and uric acid levels were altered. This indicated that increased body weight and fat as well as alteration sin glucose tolerance, hyperinsulinemia and hyperuricemia, may be associated with the biphasic nociceptive response. Drug Dev Res 77 : 258-266, 2016. © 2016 Wiley Periodicals, Inc.

Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain Depend on the Ratio used in Combination in Rats.

Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc.

Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co-Administration in an Arthritic Gout-Type Pain in Rats.

Preclinical Research Drug combinations are routinely used in the treatment of pain. In drug associations, adjuvants such as caffeine, are employed with different non-steroidal anti-inflammatories drugs (NSAIDs), however, at present does not exist studies showing the effect of the combination of racemic flurbiprofen (rac-Flur) in association with caffeine. The objective of this work was to evaluate the combination of rac-Flur + caffeine oral in arthritic gout-type pain in rats. The antinociceptive effects of the rac-Flur alone and in combination with caffeine were analyzed on a pain-induced functional impairment model in rat. rac-Flur induced a dose-dependent antinociceptive effect and caffeine did not present any effect. The combination of rac-Flur and caffeine achieve a higher percentage of antinociceptive effect compared with the individual administration of rac-Flur. The dose-response curve (DRCs) shows that the combination of rac-Flur (31.6 mg/kg) + caffeine (17.8 mg/kg) exhibited the maximal antinociceptive efficacy (294.0 ± 21.2 area units), while rac-Flur alone (31.6 mg/kg) showed 207.2 ± 35.2 au, thus indicating an increase in efficacy (potentiation). Furthermore, the DRCs of the combinations presented a displacement to the left, indicating a change in the potency. Caffeine is able to increase the effect of rac-Flur in the arthritic gout-type pain in rats. Drug Dev Res 77 : 192-198, 2016. © 2016 Wiley Periodicals, Inc.

The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016. © 2016 Wiley Periodicals, Inc.

Chitosan-Coated Silver Nanoparticles Inhibit Adherence and Biofilm Formation of Uropathogenic Escherichia coli.

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.

Synergistic Antinociceptive Effect of ß-Caryophyllene Oxide in Combination with Paracetamol, and the Corresponding Gastroprotective Activity.

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.

Gold Half-Shell-Coated Paclitaxel-Loaded PLGA Nanoparticles for the Targeted Chemo-Photothermal Treatment of Cancer.

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.

Novel Gold Nanorods@Thiolated Pectin on the Killing of HeLa Cells by Photothermal Ablation.

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.

The Additive Antinociceptive Effect of Resveratrol and Ketorolac in the Formalin Test in Mice.

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.

N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice.

OBJECTIVE: The antinociceptive pharmacological interaction between N-palmitoylethanolamide (PEA) and morphine (MOR), as well as gabapentin (GBP), was investigated to obtain synergistic antinociception at doses where side effects were minimal. In addition, the possible antinociceptive mechanism of PEA + MOR or PEA + GBP combinations was explored. METHODS: Individual dose-response curves (DRCs) of PEA, MOR and GBP were evaluated in female mice in which intraplantar nociception was induced with 2% formalin. Isobolographic method was used to detect the pharmacological interaction in the combination of PEA + MOR or PEA + GBP. KEY FINDINGS: The ED50 was calculated from the DRC; the order of potency was MOR > PEA > GBP. The isobolographic analysis was obtained at a 1:1 ratio to determine the pharmacological interaction. The experimental values of flinching (PEA + MOR, Zexp = 2.72 ± 0.2 µg/paw and PEA + GBP Zexp = 2.77 ± 0.19 µg/paw) were significantly lower than those calculated theoretically (PEA + MOR Zadd = 7.78 ± 1.07 and PEA + GBP Zadd = 24.05 ± 1.91 µg/paw), resulting in synergistic antinociception. Pretreatment with GW6471 and naloxone demonstrated that peroxisome proliferator-activated receptor alpha (PPARα) and opioid receptors are involved in both interactions. CONCLUSIONS: These results suggest that MOR and GBP synergistically enhance PEA-induced antinociception through PPARα and opioid receptor mechanisms. Furthermore, the results suggest that combinations containing PEA with MOR or GBP could be of interest in aiding the treatment of inflammatory pain.

Physicochemical characteristics of protein-NP bioconjugates: the role of particle curvature and solution conditions on human serum albumin conformation and fibrillogenesis inhibition.

Gold nanoparticles (Au NPs) from 5 to 100 nm in size synthesized with HAuCl(4) and sodium citrate were complexed with the plasma protein human serum albumin (HSA). Size, surface charge, and surface plasmon bands of the Au NPs are largely modified by the formation of a protein corona via electrostatic interactions and hydrogen bonding as revealed by thermodynamic data. Negative values of the entropy of binding suggested a restriction in the biomolecule mobility upon adsorption. The structure of the adsorbed protein molecules is slightly affected by the interaction with the metal surface, but this effect is enhanced as the NP curvature decreases. Also, it is observed that the protein molecules adsorbed onto the NP surface are more resistant to complete thermal denaturation than free protein ones as deduced from the increases in the melting temperature of the adsorbed protein. Differences in the conformations of the adsorbed protein molecules onto small (<40 nm) and large NPs were observed on the basis of ζ-potential data and FTIR spectroscopy, also suggesting a better resistance of adsorbed protein molecules to thermal denaturing conditions. We think this enhanced protein stability is responsible for a reduced formation of HSA amyloid-like fibrils in the presence of small Au NPs under HSA fibrillation conditions.

Deep Learning for Infant Cry Recognition.

Recognizing why an infant cries is challenging as babies cannot communicate verbally with others to express their wishes or needs. This leads to difficulties for parents in identifying the needs and the health of their infants. This study used deep learning (DL) algorithms such as the convolutional neural network (CNN) and long short-term memory (LSTM) to recognize infants' necessities such as hunger/thirst, need for a diaper change, emotional needs (e.g., need for touch/holding), and pain caused by medical treatment (e.g., injection). The classical artificial neural network (ANN) was also used for comparison. The inputs of ANN, CNN, and LSTM were the features extracted from 1607 10 s audio recordings of infants using mel-frequency cepstral coefficients (MFCC). Results showed that CNN and LSTM both provided decent performance, around 95% in accuracy, precision, and recall, in differentiating healthy and sick infants. For recognizing infants' specific needs, CNN reached up to 60% accuracy, outperforming LSTM and ANN in almost all measures. These results could be applied as indicators for future applications to help parents understand their infant's condition and needs.

Polymeric nanoparticles for the delivery of Sonoran desert propolis: Synthesis, characterization and antiproliferative activity on cancer cells.

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.

Design and selection of peptides to block the SARS-CoV-2 receptor binding domain by molecular docking.

The novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently one of the most contagious viruses in existence and the cause of the worst pandemic in this century, COVID-19. SARS-CoV-2 infection begins with the recognition of the cellular receptor angiotensin converting enzyme-2 by its spike glycoprotein receptor-binding domain (RBD). Thus, the use of small peptides to neutralize the infective mechanism of SARS-CoV-2 through the RBD is an interesting strategy. The binding ability of 104 peptides (University of Nebraska Medical Center's Antimicrobial Peptide Database) to the RBD was assessed using molecular docking. Based on the molecular docking results, peptides with great affinity to the RBD were selected. The most common amino acids involved in the recognition of the RBD were identified to design novel peptides based on the number of hydrogen bonds that were formed. At physiological pH, these peptides are almost neutral and soluble in aqueous media. Interestingly, several peptides showed the capability to bind to the active surface area of the RBD of the Wuhan strain, as well as to the RBD of the Delta variant and other SARS-Cov-2 variants. Therefore, these peptides have promising potential in the treatment of the COVID-19 disease caused by different variants of SARS-CoV-2. This research work will be focused on the molecular docking of peptides by molecular dynamics, in addition to an analysis of the possible interaction of these peptides with physiological proteins. This methodology could be extended to design peptides that are active against other viruses.

Antibacterial and Antioxidant Properties of Extracts of Yucca Baccata, a Plant of Northwestern Mexico, against Pathogenic Bacteria.

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.