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Journal of Materials Chemistry. B Jul 2024Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a...
Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength hydrogen bonds. Having an average diameter of 220 μm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.
PubMed: 38958038
DOI: 10.1039/d4tb00889h -
Faraday Discussions Jul 2024Biocatalysis is a rapidly evolving field with increasing impact in organic synthesis, chemical manufacturing and medicine. The reflected the current state of...
Biocatalysis is a rapidly evolving field with increasing impact in organic synthesis, chemical manufacturing and medicine. The reflected the current state of biocatalysis, covering the design of enzymatic activities, but especially methods for the improvement of enzymes targeting a broad range of applications (, hydroxylations by P450 monooxygenases, enzymatic deprotection of organic compounds under mild conditions, synthesis of chiral intermediates, plastic degradation, silicone polymer synthesis, and peptide synthesis). Central themes have been how to improve an enzyme using methods of rational design and directed evolution, informed by computer modelling and machine learning, and the incorporation of new catalytic functionalities to create hybrid and artificial enzymes.
PubMed: 38958033
DOI: 10.1039/d4fd00127c -
Headache Jul 2024The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive...
The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication-overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo-controlled trials to rigorously assess this strategy.
PubMed: 38957980
DOI: 10.1111/head.14775 -
Hypertension (Dallas, Tex. : 1979) Jul 2024Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who...
BACKGROUND
Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.
METHODS
In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.
RESULTS
Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; =0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively.
CONCLUSIONS
In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.
PubMed: 38957975
DOI: 10.1161/HYPERTENSIONAHA.124.22876 -
Nucleic Acid Therapeutics Jul 2024Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an...
Although has been considered an undruggable target, alterations confer poor prognosis in many pediatric and adult cancers. The novel -specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with -positive tumors.
PubMed: 38957973
DOI: 10.1089/nat.2024.0005 -
A Snake Venom Peptide and Its Derivatives Prevent Aβ Aggregation and Eliminate Toxic Aβ Aggregates .ACS Chemical Neuroscience Jul 2024Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its...
Over a century has passed since Alois Alzheimer first described Alzheimer's disease (AD), and since then, researchers have made significant strides in understanding its pathology. One key feature of AD is the presence of amyloid-β (Aβ) peptides, which form amyloid plaques, and therefore, it is a primary target for treatment studies. Naturally occurring peptides have garnered attention for their potential pharmacological benefits, particularly in the central nervous system. In this study, nine peptide derivatives of Crotamine, a polypeptide from Rattlesnake venom, as well as one d-enantiomer, were evaluated for their ability to modulate Aβ aggregation through various assays such as ThT, QIAD, SPR, and sFIDA. All tested peptides were able to decrease Aβ aggregation and eliminate Aβ aggregates. Additionally, all of the peptides showed an affinity for Aβ. This study is the first to describe the potential of crotamine derivative peptides against Aβ aggregation and to identify a promising d-peptide that could be used as an effective pharmacological tool against AD in the future.
PubMed: 38957957
DOI: 10.1021/acschemneuro.4c00089 -
Journal of Agricultural and Food... Jul 2024This study investigated the mechanism underlying the flavor improvement observed during fermentation of a pea protein-based beverage using NCC533. A combination of...
This study investigated the mechanism underlying the flavor improvement observed during fermentation of a pea protein-based beverage using NCC533. A combination of sensomics and sensoproteomics approach revealed that the fermentation process enriched or generated well-known basic taste ingredients, such as amino acids, nucleotides, organic acids, and dipeptides, besides six new taste-active peptide sequences that enhance kokumi and umami notes. The six new umami and kokumi enhancing peptides, with human recognition thresholds ranging from 0.046 to 0.555 mM, are produced through the degradation of 's storage protein. Our findings suggest that compounds derived from fermentation enhance umami and kokumi sensations and reduce bitterness, thus improving the overall flavor perception of pea proteins. In addition, the analysis of intraspecific variations in the proteolytic activity of and the genome-peptidome correlation analysis performed in this study point at cell-wall-bound proteinases such as PrtP and PrtM as the key genes necessary to initiate the flavor improving proteolytic cascade. This study provides valuable insights into the molecular mechanisms underlying the flavor improvement of pea protein during fermentation and identifies potential future research directions. The results highlight the importance of combining fermentation and senso(proteo)mics techniques in developing tastier and more palatable plant-based protein products.
PubMed: 38957928
DOI: 10.1021/acs.jafc.4c02317 -
Regenerative Medicine Jul 2024Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after...
Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after repair of the sciatic nerve in healthy Wistar rats. PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages.
PubMed: 38957920
DOI: 10.1080/17460751.2024.2361515 -
Organic & Biomolecular Chemistry Jul 2024Phosphatidic acid and phosphatidylserine are anionic phospholipids with emerging signalling roles in cells. Determination of how phosphatidic acid and phosphatidylserine...
Phosphatidic acid and phosphatidylserine are anionic phospholipids with emerging signalling roles in cells. Determination of how phosphatidic acid and phosphatidylserine change location and quantity in cells over time requires selective fluorescent sensors that can distinguish these two anionic phospholipids. However, the design of such synthetic sensors that can selectively bind and respond to a single phospholipid within the complex membrane milieu remains challenging. In this work, we present a simple and robust strategy to control the selectivity of synthetic sensors for phosphatidic acid and phosphatidylserine. By changing the coordination metal of a dipicolylamine (DPA) ligand from Zn(II) to Ni(II) on the same synthetic sensor with a peptide backbone, we achieve a complete switch in selectivity from phosphatidic acid to phosphatidylserine in model lipid membranes. Furthermore, this strategy was largely unaffected by the choice and the position of the fluorophores. We envision that this strategy will provide a platform for the rational design of targeted synthetic phospholipid sensors to probe plasma and intracellular membranes.
PubMed: 38957899
DOI: 10.1039/d4ob00418c -
Ghana Medical Journal Dec 2023The study assessed gustatory functions in patients with primary hypothyroidism who are euthyroid on supplemental hormone therapy with levothyroxine over six months'...
OBJECTIVES
The study assessed gustatory functions in patients with primary hypothyroidism who are euthyroid on supplemental hormone therapy with levothyroxine over six months' duration and to evaluate the association of gustatory dysfunction, if any, with the serum TSH levels.
DESIGN
This analytical community-based cross-sectional study was conducted in April 2021, following participants' ethical approval and written informed consent.
SETTING
The study was conducted in a tertiary health care centre in Bangalore, Karnataka, India.
PARTICIPANTS
Sixty-eight subjects participated in this study: 34 primary hypothyroid patients and an equal number of healthy controls.
INTERVENTIONS
Gustatory sensations were assessed by the triple drop test, and scores were given depending on the identification of the tastants (sweet, sour, salty, and bitter). The taste scores were compared, and the association between TSH levels and gustatory parameters were evaluated.
RESULTS
Overall taste scores were lesser in hypothyroid patients. This finding depicted that their taste thresholds were increased and were statistically significant (p < 0.001), though the association between the degree of hypogeusia and TSH levels was not statistically significant.
CONCLUSION
Patients with primary hypothyroidism can suffer from hypogeusia, which may revert to normal once they achieve euthyroid status with levothyroxine supplementation. However, this has not been conclusively shown in studies. Our study concluded that hypogeusia was present in primary hypothyroidism despite patients being euthyroid on hormone supplementation, and it was not dependent on the serum TSH levels.
FUNDING
None declared.
Topics: Humans; Hypothyroidism; Cross-Sectional Studies; Female; Male; Thyroxine; Adult; Middle Aged; Thyrotropin; Taste Disorders; India; Case-Control Studies
PubMed: 38957847
DOI: 10.4314/gmj.v57i4.3