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C60@lysozyme showed significant visible light-induced singlet oxygen generation in water, indicating the potential of this hybrid as an agent for photodynamic therapy. The reactive oxygen species (ROS) concentration generated by C60@lysozyme during irradiation depends on the light source, the irradiation time and the concentration of the hybrid. C60@lysozyme significantly reduced the HeLa cell viability in response to visible light irradiation. The generation of H2O2, due to the photoactivity of C60@lysozyme, causes cell death via easy permeation of hydrogen peroxide through the cell membrane and activation of endogenous ROS production. [ABSTRACT FROM AUTHOR]

The authors performed a review of the literature to evaluate the efficacy of low level laser therapy (LLLT) for the treatment of temporomandibular disorders (TMD). Selection criteria included: 1) human subjects, 2) articles written in English, and 3) randomized placebo-controlled trials. Evaluation was performed according to the CONSORT 2010 criteria. A total of 14 articles were included in the review. Studies varied considerably in terms of methodological design, particularly regarding the site of application of the laser beam, the number of applications performed, their duration, the laser beam features (wavelength, frequency, output, dosage), and outcome measures. The outcome of the trials was controversial and not particularly related to any features of the laser beam, to the number of laser applications, and their duration. Based on the results of this review no definitive conclusions can be drawn on the efficacy of LLLT for the treatment of TMD. Many methodological differences among the studies, especially regarding the number and duration of laser applications and characteristics of the laser beam (wavelength, frequency, output), do not allow for standardized guidelines for effective treatment with LLLT. The only indication seems to be that LLLT is probably more effective for the treatment of TMJ disorders, and less effective for the treatment of masticatory muscle disorders. [ABSTRACT FROM AUTHOR]

Purpose: Temporomandibular Joint Arthralgia (TMJA) in the absence of osteoarthritis has not been thoroughly studied. We aimed to investigate the presence of comorbid bodily pain conditions (CBPC) in patients with TMJA with and without TMJOA and hypothesized that TMJOA is not associated with a higher presence of CBPC. Methods: This is a retrospective study involving patients at the University of North Carolina Orofacial Pain Clinic between 2010 and 2014 with TMJA according to the RDC/TMD criteria [1]. Cases fulfilled the Ahmad classification for TMJOA [2], and had TMJA (TMJA+OA), while controls had TMJA only (TMJA-OA). Data was collected from reports of Cone-Beam Computerized Tomography (CBCT). CBPC were self-reported. Results: Twenty-eight cases (TMJA+OA) and 25 controls (TMJA-OA) were included. The mean age of cases and controls (P = 0.027) and mean pain duration differed (P = 0.031). However, the gender distribution (P = 0.552), mean pain intensity (P = 0.381), mean number of painful muscles upon palpation (P = 0.759) and mean number of CBPC (P = 0.575) were not different. At least one CBPC was reported by 68% cases and 72% control subjects (P = 0.743). Conclusions: In this group of patients with TMJA, the presence of CBPC was high and not associated with the presence of TMJOA. This finding suggests that CBPC and TMJOA occur independently.

Thiophene-based nanoparticles (TNPs) are promising therapeutic and imaging agents. Here, using an innovative phage-templated synthesis, a strategy able to bypass the current limitations of TNPs in nanomedicine applications is proposed. The phage capsid is decorated with oligothiophene derivatives, transforming the virus in a 1D-thiophene nanoparticle (1D-TNP). A precise control of the shape/size of the nanoparticles is obtained exploiting the well-defined morphology of a refactored filamentous M13 phage, engineered by phage display to selectively recognize the Epidermal Growth Factor Receptor (EGFR). The tropism of the phage is maintained also after the bioconjugation of the thiophene molecules on its capsid. Moreover, the 1D-TNP proved highly fluorescent and photoactive, generating reactive oxygen species through both type I and type II mechanisms. The phototheranostic properties of this platform are investigated on biosystems presenting increasing complexity levels, from in vitro cancer cells in 2D and 3D architectures, to the in vivo tissue-like model organism Hydra vulgaris. The phage-templated 1D-TNP showed photocytotoxicity at picomolar concentrations, and the ability to deeply penetrate 3D spheroids and Hydra tissues. Collectively the results indicate that phage-templated synthesis of organic nanoparticles represents a general strategy, exploitable in many diagnostic and therapeutic fields based on targeted imaging and light mediated cell ablation., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13 CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13 CC -RB bioconjugate were investigated on CC cells. We show that upon irradiation M13 CC -RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13 CC -RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13 CC -RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies., (© 2024. The Author(s).)

In the present study, we aimed to assess the frequency of and the relationships between alexithymia, burnout, and hopelessness in a large sample of healthcare workers (HCWs) during the third wave of COVID-19 in Italy. Alexithymia was evaluated by the Italian version of the 20-item Toronto Alexithymia Scale (TAS-20) and its subscales Difficulty in Identifying Feelings (DIF), Difficulty in Describing Feelings (DDF), and Externally Oriented Thinking (EOT), burnout was measured with the scales emotional exhaustion (EE), depersonalisation (DP), and personal accomplishment (PA) of the Maslach Burnout Test (MBI), hopelessness was measured using the Beck Hopelessness Scale (BHS), and irritability (IRR), depression (DEP), and anxiety (ANX) were evaluated with the Italian version of the Irritability' Depression' Anxiety Scale (IDA). This cross-sectional study recruited a sample of 1445 HCWs from a large urban healthcare facility in Italy from 1 May to 31 June 2021. The comparison between individuals that were positive ( n = 214, 14.8%) or not for alexithymia ( n = 1231, 85.2%), controlling for age, gender, and working seniority, revealed that positive subjects showed higher scores on BHS, EE, DP IRR, DEP, ANX, DIF, DDF, and EOT and lower on PA than the not positive ones ( p < 0.001). In the linear regression model, higher working seniority as well as higher EE, IRR, DEP, ANX, and DDF scores and lower PA were associated with higher hopelessness. In conclusion, increased hopelessness was associated with higher burnout and alexithymia. Comprehensive strategies should be implemented to support HCWs' mental health and mitigate the negative consequences of alexithymia, burnout, and hopelessness.

Semiconducting single walled carbon nanotubes (SWCNTs) are promising materials for biosensing applications with electrolyte-gated transistors (EGT). However, to be employed in EGT devices, SWCNTs often require lengthy solution-processing fabrication techniques. Here, we introduce a simple solution-based method that allows fabricating EGT devices from stable dispersions of SWCNTs/bovine serum albumin (BSA) hybrids in water. The dispersion is then deposited on a substrate allowing the formation of a SWCNTs random network as the semiconducting channel. We demonstrate that this methodology allows the fabrication of EGT devices with electric performances that allow their use in biosensing applications. We demonstrate their application for the detection of cortisol in solution, upon gate electrode functionalization with anti-cortisol antibodies. This is a robust and cost-effective methodology that sets the ground for a SWCNT/BSA-based biosensing platform that allows overcoming many limitations of standard SWCNTs biosensor fabrications., (© 2023 Wiley-VCH GmbH.)

Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very few efforts have been made to combine the advantages of both approaches in a modular, retargetable platform. Here, we foster the M13 bacteriophage as a multifunctional scaffold, enabling the selective photodynamic killing of bacteria. We took advantage of the well-defined molecular biology of M13 to functionalize its capsid with hundreds of photo-activable Rose Bengal sensitizers and contemporarily target this light-triggerable nanobot to specific bacterial species by phage display of peptide targeting moieties fused to the minor coat protein pIII of the phage. Upon light irradiation of the specimen, the targeted killing of diverse Gram(-) pathogens occurred at subnanomolar concentrations of the phage vector. Our findings contribute to the development of antimicrobials based on targeted and triggerable phage-based nanobiotherapeutics., Competing Interests: There are no conflicts to declare., (© 2023 The Author(s).)

Chlorin e6 (Ce6) and fullerene (C 60 ) are among the most used photosensitizers (PSs) for photodynamic therapy (PDT). Through the combination of the chemical and photophysical properties of Ce6 and C 60 , in principle, we can obtain an "ideal" photosensitizer that is able to bypass the limitations of the two molecules alone, i.e., the low cellular uptake of Ce6 and the scarce solubility and absorption in the red region of the C 60 . Here, we synthesized and characterized a Ce6-C 60 dyad. The UV-Vis spectrum of the dyad showed the typical absorption bands of both fullerene and Ce6, while a quenching of Ce6 fluorescence was observed. This behavior is typical in the formation of a fullerene-antenna system and is due to the intramolecular energy, or electron transfer from the antenna (Ce6) to the fullerene. Consequently, the Ce6-C 60 dyad showed an enhancement in the generation of reactive oxygen species (ROS). Flow cytometry measurements demonstrated how the uptake of the Ce6 was strongly improved by the conjugation with C 60 . The Ce6-C 60 dyad exhibited in A431 cancer cells low dark toxicity and a higher PDT efficacy than Ce6 alone, due to the enhancement of the uptake and the improvement of ROS generation.

Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS). Applying a reverse docking approach, here, we identified a number of blood transport proteins able to bind and disperse monomolecularly mTHPC, namely apohemoglobin, apomyoglobin, hemopexin, and afamin. We validated the computational results synthesizing the mTHPC-apomyoglobin complex (mTHPC@apoMb) and demonstrated that the protein monodisperses mTHPC in a physiological environment. The mTHPC@apoMb complex preserves the imaging properties of the molecule and improves its ability to produce ROS via both type I and type II mechanisms. The effectiveness of photodynamic treatment using the mTHPC@apoMb complex was then demonstrated in vitro. Blood transport proteins can be used as molecular "Trojan horses" in cancer cells by conferring mTHPC (i) water solubility, (ii) monodispersity, and (iii) biocompatibility, ultimately bypassing the current limitations of mTHPC.

Chlorin e6 (Ce6) is among the most used sensitizers in photodynamic (PDT) and sonodynamic (SDT) therapy; its low solubility in water, however, hampers its clinical exploitation. Ce6 has a strong tendency to aggregate in physiological environments, reducing its performance as a photo/sono-sensitizer, as well as yielding poor pharmacokinetic and pharmacodynamic properties. The interaction of Ce6 with human serum albumin (HSA) (i) governs its biodistribution and (ii) can be used to improve its water solubility by encapsulation. Here, using ensemble docking and microsecond molecular dynamics simulations, we identified the two Ce6 binding pockets in HSA, i.e., the Sudlow I site and the heme binding pocket, providing an atomistic description of the binding. Comparing the photophysical and photosensitizing properties of Ce6@HSA with respect to the same properties regarding the free Ce6, it was observed that (i) a red-shift occurred in both the absorption and emission spectra, (ii) a maintaining of the fluorescence quantum yield and an increase of the excited state lifetime was detected, and (iii) a switch from the type II to the type I mechanism in a reactive oxygen species (ROS) production, upon irradiation, took place.

Objective: To evaluate the hypothesis that dental arch form and inter-canine, inter-premolar, and inter-molar widths differ between OSAS patients and non-snoring, non-apneic controls., Methods: Dental digital models from 64 OSAS patients and 64 control subjects were used to obtain dental arch forms and to compare them between the two groups. Arch forms were extracted from the lower arch models using a professional graphics program and an orthodontic digital template. Through an orthodontic software, inter-molar, inter-premolar, and inter-canine widths were measured for both upper and lower arches., Results: The dental arch forms distribution differed between OSAS patients and controls. OSAS patients had reduced inter-canine, inter-premolar, and inter-molar widths for both arches compared to controls., Discussion: These results suggest that OSAS patients have narrower and more tapered arches than controls. Dental arch morphology and interdental widths differ between OSAS and control groups, supporting the hypothesis that they are an etiological factor.

The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range, making it a potential PS. Here, we exploited the intrinsic photosensitizing properties of doxorubicin to enhance its anticancer activity in leukemia, breast, and epidermoid carcinoma cells, upon irradiation. Light can selectively trigger the local generation of reactive oxygen species (ROS), following photophysical pathways. Doxorubicin showed a concentration-dependent ability to generate peroxides and singlet oxygen upon irradiation. The underlying mechanisms leading to the increase in its cytotoxic activity were intracellular ROS generation and the induction of necrotic cell death. The nuclear localization of doxorubicin represents an added value for its use as a PS. The use of doxorubicin in PCT, simultaneously acting as a chemotherapeutic agent and a PS, may allow (i) an increase in the anticancer effects of the drug, and (ii) a decrease in its dose, and thus, its dose-related adverse effects.

Temoporfin (mTHPC) is approved in Europe for the photodynamic treatment of head and neck squamous cell carcinoma (HNSCC). Although it has a promising profile, its lipophilic character hampers the full exploitation of its potential due to high tendency of aggregation and a reduced ROS generation that compromise photodynamic therapy (PDT) efficacy. Moreover, for its clinical administration, mTHPC requires the presence of ethanol and propylene glycol as solvents, often causing adverse effects in the site of injection. In this paper we explored the efficiency of a new mTHPC formulation that uses human serum albumin (HSA) to disperse the photosensitizer in solution (mTHPC@HSA), investigating its anticancer potential in two HNSCC cell lines. Through a comprehensive characterization, we demonstrated that mTHPC@HSA is stable in physiological environment, does not aggregate, and is extremely efficient in PDT performance, due to its high singlet oxygen generation and the high dispersion as monomolecular form in HSA. This is supported by the computational identification of the specific binding pocket of mTHPC in HSA. Moreover, mTHPC@HSA-PDT induces cytotoxicity in both HNSCC cell lines, increasing intracellular ROS generation and the number of γ-H2AX foci, a cellular event involved in the global response to cellular stress. Taken together these results highlight the promising phototoxic profile of the complex, prompting further studies to assess its clinical potential.

Objective: To investigate the use of applied kinesiology in the field of dentistry., Methods: A review of the literature was carried out looking for all articles written on the topic. PubMed, Ovid Medline, and The Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched., Results: Only one study was retrieved on the use of applied kinesiology in temporomandibular disorder patients, and only one study was published on dental material testing. A change in muscle strength associated with changes in dental occlusion has been observed in many of the articles selected., Discussion: The use of applied kinesiology for the diagnosis and treatment of pathologies in the field of dentistry is not supported by scientific evidence. However, a relationship between dental occlusion or maxillo-mandibular relationship and isometric muscle strength has been noted.

Fullerenes are considered excellent photosensitizers, being highly suitable for photodynamic therapy (PDT). A lack of water solubility and low biocompatibility are, in many instances, still hampering the full exploitation of their potential in nanomedicine. Here, we used human serum albumin (HSA) to disperse fullerenes by binding up to five fullerene cages inside the hydrophobic cavities. Albumin was bioconjugated with folic acid to specifically address the folate receptors that are usually overexpressed in several solid tumors. Concurrently, tetramethylrhodamine isothiocyanate, TRITC, a tag for imaging, was conjugated to C 60 @HSA in order to build an effective phototheranostic platform. The in vitro experiments demonstrated that: (i) HSA disperses C 60 molecules in a physiological environment, (ii) HSA, upon C 60 binding, maintains its biological identity and biocompatibility, (iii) the C 60 @HSA complex shows a significant visible-light-induced production of reactive oxygen species, and (iv) folate bioconjugation improves both the internalization and the PDT-induced phototoxicity of the C 60 @HSA complex in HeLa cells.

The chemical functionalization of polysaccharides to obtain functional materials has been of great interest in the last decades. This traditional synthetic approach has drawbacks, such as changing the crystallinity of the material or altering its morphology or texture. These modifications are crucial when a biogenic matrix is exploited for its hierarchical structure. In this work, the use of lectins and carbohydrate-binding proteins as supramolecular linkers for polysaccharide functionalization is proposed. As proof of concept, a deproteinized squid pen, a hierarchically-organized β-chitin matrix, was functionalized using a dye (FITC) labeled lectin; the lectin used was the wheat germ agglutinin (WGA). It has been observed that the binding of this functionalized protein homogenously introduces a new property (fluorescence) into the β-chitin matrix without altering its crystallographic and hierarchical structure. The supramolecular functionalization of polysaccharides with protein/lectin molecules opens up new routes for the chemical modification of polysaccharides. This novel approach can be of interest in various scientific fields, overcoming the synthetic limits that have hitherto hindered the technological exploitation of polysaccharides-based materials.

Photodynamic therapy (PDT) is a potential synergistic approach to chemotherapy for treating ovarian cancer, the most lethal gynecologic malignancy. Here we used M13 bacteriophage as a targeted vector for the efficient photodynamic killing of SKOV3 and COV362 cells. The M13 phage was refactored (M13 r ) to display an EGFR binding peptide in its tip that is frequently overexpressed in ovarian cancer. The refactored phage was conjugated with chlorin e6 (Ce6), one of the most widely used photosensitizers (M13 r -Ce6). The new platform, upon irradiation, generated ROS by type I mechanism and showed activity in killing SKOV3 and COV362 cells even at concentrations in which Ce6 alone was ineffective. A microscopy analysis demonstrated an enhanced cellular uptake of M13 r -Ce6 compared to free Ce6 and its mitochondrial localization. Western blot analysis revealed significant downregulation in the expression of EGFR in cells exposed to M13 r -Ce6 after PDT. Following PDT treatment, autophagy induction was supported by an increased expression of LC3II, along with a raised autophagic fluorescent signal, as observed by fluorescence microscopy analysis for autophagosome visualization. As a conclusion we have herein proposed a bacteriophage-based receptor targeted photodynamic therapy for EGFR-positive ovarian cancer., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Photodynamic therapy (PDT) represents a promising therapeutic modality for cancer. Here we used an orthogonal nanoarchitectonics approach (genetic/chemical) to engineer M13 bacteriophages as targeted vectors for efficient photodynamic killing of cancer cells. M13 was genetically refactored to display on the phage tip a peptide (SYPIPDT) able to bind the epidermal growth factor receptor (EGFR). The refactored M13 EGFR phages demonstrated EGFR-targeted tropism and were internalized by A431 cancer cells, that overexpress EGFR. Using an orthogonal approach to the genetic display, M13 EGFR phages were then chemically modified, conjugating hundreds of Rose Bengal (RB) photosensitizing molecules on the capsid surface, without affecting the selective recognition of the SYPIPDT peptides. Upon internalization, the M13 EGFR -RB derivatives generated intracellularly reactive oxygen species, activated by an ultralow intensity white light irradiation. The killing activity of cancer cells is observed at picomolar concentrations of the M13 EGFR phage.

The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of cancers. In recent years, photodynamic therapy (PDT) has gained increased interest as a non-invasive cancer treatment. In PDT, a photosensitizer is excited by light to produce reactive oxygen species, resulting in local cytotoxicity. One of the critical aspects of PDT is to selectively transport enough photosensitizers to the tumors environment. Accordingly, an increasing number of strategies have been devised to foster EGFR-targeted PDT. Herein, we review the recent nanobiotechnological advancements that combine the promise of PDT with EGFR-targeted molecular cancer therapy. We recapitulate the chemistry of the sensitizers and their modes of action in PDT, and summarize the advantages and pitfalls of different targeting moieties, highlighting future perspectives for EGFR-targeted photodynamic treatment of cancer.

Objective : To investigate the role of oral myofunctional therapy for the treatment of temporomandibular disorders. Methods : A search of the literature was carried out looking for randomized controlled trials performed on humans and written in English, Italian, French, and Arabic. Results : Four randomized controlled trials were found and evaluated by using the Study Quality Assessment Tool of the National Institute for Health and Clinical Excellence.Oral myofunctional therapy was shown to be effective for the treatment of temporomandibular disorders, alone or associated with other treatments, in three out of four studies, with significant reduction of pain intensity when compared to other conservative treatments and no treatment. Discussion : Even though scientific evidence is weak, oral myofunctional therapy appears to be effective for the treatment of temporomandibular disorders with favorable cost-benefit and risk-benefit ratios.

The electronic, optical, and redox properties of thiophene-based materials have made them pivotal in nanoscience and nanotechnology. However, the exploitation of oligothiophenes in photodynamic therapy is hindered by their intrinsic hydrophobicity that lowers their biocompatibility and availability in water environments. Here, we developed human serum albumin (HSA)-oligothiophene bioconjugates that afford the use of insoluble oligothiophenes in physiological environments. UV-vis and electrophoresis proved the conjugation of the oligothiophene sensitizers to the protein. The bioconjugate is water-soluble and biocompatible, does not have any "dark toxicity", and preserves HSA in the physiological monomeric form, as confirmed by dynamic light scattering and circular dichroism measurements. In contrast, upon irradiation with ultralow light doses, the bioconjugate efficiently produces reactive oxygen species (ROS) and leads to the complete eradication of cancer cells. Real-time monitoring of the photokilling activity of the HSA-oligothiophene bioconjugate shows that living cells "explode" upon irradiation. Photodependent and dose-dependent apoptosis is one of the primary mechanisms of cell death activated by bioconjugate irradiation. The bioconjugate is a novel theranostic platform able to generate ROS intracellularly and provide imaging through the fluorescence of the oligothiophene. It is also a real-time self-reporting system able to monitor the apoptotic process. The induced phototoxicity is strongly confined to the irradiated region, showing localized killing of cancer cells by precise light activation of the bioconjugate., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Colorectal cancer (CRC) is a widespread and lethal disease. Relapses of the disease and metastasis are very common in instances of CRC, so adjuvant therapies have a crucial role in its treatment. Systemic toxic effects and the development of resistance during therapy limit the long-term efficacy of existing adjuvant therapeutic approaches. Consequently, the search for alternative strategies is necessary. Photothermal therapy (PTT) represents an innovative treatment for cancer with great potential. Here, we synthesize branched gold nanoparticles (BGNPs) as attractive agents for the photothermal eradication of colon cancer cells. By controlling the NP growth process, large absorption in the first NIR biological window was obtained. The FBS dispersed BGNPs are stable in physiological-like environments and show an extremely efficient light-to-heat conversion capability when irradiated with an 808-nm laser. Sequential cycles of heating and cooling do not affect the BGNP stability. The uptake of BGNPs in colon cancer cells was confirmed using flow cytometry and confocal microscopy, exploiting their intrinsic optical properties. In dark conditions, BGNPs are fully biocompatible and do not compromise cell viability, while an almost complete eradication of colon cancer cells was observed upon incubation with BGNPs and irradiation with an 808-nm laser source. The PTT treatment is characterized by an extremely rapid onset of action that leads to cell membrane rupture by induced hyperthermia, which is the trigger that promotes cancer cell death.

Bionic composites are an emerging class of materials produced exploiting living organisms as reactors to include synthetic functional materials in their native and highly performing structures. In this work, single wall carboxylated carbon nanotubes (SWCNT-COOH) were incorporated within the roots of living plants of Arabidopsis thaliana . This biogenic synthetic route produced a bionic composite material made of root components and SWCNT-COOH. The synthesis was possible exploiting the transport processes existing in the plant roots. Scanning electrochemical microscopy (SECM) measurements showed that SWCNT-COOH entered the vascular bundles of A. thaliana roots localizing within xylem vessels. SWCNT-COOH preserved their electrical properties when embedded inside the root matrix, both at a microscopic level and a macroscopic level, and did not significantly affect the mechanical properties of A. thaliana roots., (Copyright © 2020 Magnabosco, Pantano, Rapino, Di Giosia, Valle, Taxis, Sparla, Falini, Pugno and Calvaresi.)

Propranolol is a nonselective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18 to 65 years with temporomandibular disorder myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100). Efficacy was analyzed as a mean change in FPI from randomization to week 9 and as the proportion of participants with ≥30% or ≥50% reductions in FPI at week 9. Regression models tested for treatment-group differences adjusting for study site, sex, race, and FPI at randomization. Of 299 participants screened, 200 were randomized; 199 had at least one postrandomization FPI measurement and were included in intention-to-treat analysis. At week 9, model-adjusted reductions in mean FPI did not differ significantly between treatment groups (-1.8, 95% CL: -6.2, 2.6; P = 0.41). However, the proportion with a ≥30% reduction in FPI was significantly greater for propranolol (69.0%) than placebo (52.6%), and the associated number-needed-to-treat was 6.1 (P = 0.03). Propranolol was likewise efficacious for a ≥50% reduction in FPI (number-needed-to-treat = 6.1, P = 0.03). Adverse event rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group. Propranolol was not different from placebo in reducing mean FPI but was efficacious in achieving ≥30% and ≥50% FPI reductions after 9 weeks of treatment among temporomandibular disorder participants.

The preferred spatial orientation of single-wall carbon nanotubes (SWCNTs) in their interaction with enzymes determines their behavior either as nano-supports or as inhibitors. α -chymotrypsin (α-CT) is considered a serine protease model for studying nanomaterial/proteases interactions. The interaction of α-CT with pristine single-wall carbon nanotubes is still unknown. Here α-CT/SWCNT hybrids are synthesized and characterized. Spectroscopic, microscopic and kinetic measurements, coupled to molecular dynamics simulations, provide a detailed description of the interaction between α-CT and SWCNTs. The SWCNT binding pocket was unambiguously identified. A perfect match is observed with the crevice structure of the α-CT substrate binding pocket. The activity of α-CT, upon SWCNT binding, is dramatically reduced, as expected by the interaction of the SWCNT in the active site of the protein. π-π stacking between aromatic residues and the conjugated surface of SWCNT governs α-CT/SWCNT interactions. An important role in the bonding appears also for purely hydrophobic residues and with residues able to establish surfactant-like interactions. The secondary structure of α-CT and the catalytic triad structure are not perturbed by the complex formation, on the contrary the volume of the substrate binding pocket is strongly reduced by SWCNT binding because SWCNT occupies the α-CT substrate binding site, clogging the active site., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Photodynamic therapy (PDT) is considered a very promising therapeutic modality for antimicrobial therapy. Although several studies have demonstrated that Gram-positive bacteria are very sensitive to PDT, Gram-negative bacteria are more resistant to photodynamic action. This difference is due to a different cell wall structure. Gram-negative bacteria have an outer cell membrane containing lipopolysaccharides (LPS) that hinder the binding of photosensitizer molecules, protecting the bacterial cells from chemical attacks. Combination of the lipopolysaccharides-binding activity of Concanavalin A (ConA) with the photodynamic properties of Rose Bengal (RB) holds the potential of an innovative protein platform for targeted photodynamic therapy against Gram-negative bacteria. A ConA-RB bioconjugate was synthesized and characterized. Approximately 2.4 RB molecules were conjugated per ConA monomer. The conjugation of RB to ConA determines a decrease of the singlet oxygen generation and an increase of superoxide and peroxide production. The photokilling efficacy of the ConA-RB bioconjugate was demonstrated in a planktonic culture of E. coli. Irradiation with white light from a LED lamp produced a dose-dependent photokilling of bacteria. ConA-RB conjugates exhibited a consistent improvement over RB (up to 117-fold). The improved uptake of the photosensitizer explains the enhanced PDT effect accompanying increased membrane damages induced by the ConA-RB conjugate. The approach can be readily generalized (i) using different photo/sonosensitizers, (ii) to target other pathogens characterized by cell membranes containing lipopolysaccharides (LPS)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The controlled release of cell differentiating agents is crucial in many aspects of regenerative medicine. Here we propose the use of hybrid calcite single crystals as micro-carriers for the controlled and localized release of retinoic acid, which is entrapped within the crystalline lattice. The release of retinoic acid occurs only in the proximity of stem cells, upon dissolution of the calcite hybrid crystals that are dispersed in the fibrin scaffold. These hybrid crystals provide a sustained dosage of the entrapped agent. The environment provided by this composite scaffold enables differentiation towards neuronal cells that form a three-dimensional neuronal network.