Photodynamic therapy in cancer stem cells - state of the art.

Despite significant efforts to control cancer progression and to improve oncology treatment outcomes, recurrence and tumor resistance are frequently observed in cancer patients. These problems are partly related to the presence of cancer stem cells (CSCs). Photodynamic therapy (PDT) has been developed as a therapeutic approach for solid tumors; however, it remains unclear how this therapy can affect CSCs. In this review, we focus on the effects of PDT on CSCs and the possible changes in the CSC population after PDT exposure. Tumor response to PDT varies according to the photosensitizer and light parameters employed, but most studies have reported the successful elimination of CSCs after PDT. However, some studies have reported that CSCs were more resistant to PDT than non-CSCs due to the increased efflux of photosensitizer molecules and the action of autophagy. Additionally, using different PDT approaches to target the CSCs resulted in increased sensitivity, reduction of sphere formation, invasiveness, stem cell phenotype, and improved response to chemotherapy. Lastly, although mainly limited to in vitro studies, PDT, combined with targeted therapies and/or chemotherapy, could successfully target CSCs in different solid tumors and promote the reduction of stemness, suggesting a promising therapeutic approach requiring evaluation in robust pre-clinical studies.

Photodynamic therapy for squamous cell carcinoma of the head and neck: narrative review focusing on photosensitizers.

This narrative review aimed to evaluate the effectiveness of PDT in early or advanced squamous cell carcinoma of the head and neck (SCCHN). Scopus, MEDLINE/PubMed, and Embase were searched electronically following the PRISMA protocol. Quality assessment was performed according to JBI, NIH, and AMSTAR protocols. The main outcomes evaluated were treatment response, recurrence, survival, and adverse effects. A total of 49 articles met the search criteria: 43 case series, two cohort studies, two prospective before-after clinical trials, one systematic review, and one meta-analysis. Data from 2121 SCCHN patients were included. The response to PDT was variable according to the type of photosensitizer, tumor location, and tumor stage. In general, higher complete responses rated were observed in T1/T2 SCCHN, mainly with mTHPC-mediated PDT. With regard to T3/T4 or advanced SCCHN tumors, there is no compelling evidence suggesting the effectiveness of PDT. Any adverse effects reported were well tolerated by patients. The present review suggests that PDT is a promising treatment modality for early-stage SCCHN. Although there are limitations due to the low level of evidence of the included studies, we believe that the present review could help to design robust clinical trials to determine the efficacy of PDT in SCCHN.

Silicone breast implants and connective tissue diseases: How does current evidence add to the no-association consensus? Systematic review and meta-analysis.

To evaluate the current state of the evidence regarding the association of silicone breast implantation with the onset of connective tissue diseases, constitutional symptoms, and rheumatic serological profile in adult women. A comprehensive search was carried out using MEDLINE, Embase, Web of Science and Scopus, from inception to September 2, 2020. Cohort studies assessing the clinical and serological profile of women with cosmetic breast implants were included. Meta-analyses were conducted using risk ratios. A total of 10 cohorts with overall moderate quality of evidence were included in this systematic review. Exposure to silicone breast implants was slightly associated with the development of rheumatoid arthritis [RR: 1.35; (95% CI 1.08 to 1.68); P = .008; I2 = 0%]. However, no significant differences were exhibited between the breast implant-exposed population and controls regarding the rest of the outcomes. In adult women, exposure to silicone breast implantation is not associated with the onset of constitutional symptoms and most connective tissue diseases. A marginal association with rheumatoid arthritis was exhibited, but the certainty of this result is jeopardized by the significant amount of self-reported data for this outcome. Further research is required to adequately explore the clinical significance of these results.

Photobiomodulation on trigeminal neuralgia: systematic review.

Trigeminal neuralgia is a recurrent episode of facial pain, that may be associated with other conditions such as multiple sclerosis, neoplasms, and nerve compromises or may occur due to an unknown cause. The available treatments are pharmacotherapy or surgery; however, both are susceptible to develop side effects. Photobiomodulation could be a promising alternative therapy for trigeminal neuralgia. A systematic review of literature was carried out using the PRISMA protocol, in the PubMed/MEDLINE, Embase, and Web of Science databases. Risk of bias by ROB 2.0 protocol was performed in included studies. Initially, 20 identified articles were collected varying between the years of 1983-2018, from which 6 were included. A total of 193 patients were evaluated; photobiomodulation was compared to conventional therapies, TENS, and therapy combinations with pharmacotherapy. The overall risk of bias was low, with some concerns in the randomization and double-blinding process; moreover, there are few reports in the literature. Photobiomodulation appears to be as effective as conventional therapies, being a coadjutant therapeutic opportunity for the treatment of trigeminal neuralgia.

Effects of photobiomodulation on cellular viability and cancer stem cell phenotype in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

Transcriptomic information from Pacific white shrimp (Litopenaeus vannamei) ovary and eyestalk, and expression patterns for genes putatively involved in the reproductive process.

The increased use of massive sequencing technologies has enabled the identification of several genes known to be involved in different mechanisms associated with reproduction that so far have only been studied in vertebrates and other model invertebrate species. In order to further investigate the genes involved in Litopenaeus vannamei reproduction, cDNA and SSH libraries derived from female eyestalk and gonad were produced, allowing the identification of expressed sequences tags (ESTs) that potentially have a role in the regulation of gonadal maturation. In the present study, different transcripts involved in reproduction were identified and a number of them were characterized as full-length. These transcripts were evaluated in males and females in order to establish their tissue expression profiles during developmental stages (juvenile, subadult and adult), and in the case of females, their possible association with gonad maturation was assessed through expression analysis of vitellogenin. The results indicated that the expression of vitellogenin receptor (vtgr) and minichromosome maintenance (mcm) family members in the female gonad suggest an important role during previtellogenesis. Additionally, the expression profiles of genes such as famet, igfbp and gpcr in brain tissues suggest an interaction between the insulin/insulin-like growth factor signaling pathway (IIS) and methyl farnesoate (MF) biosynthesis for control of reproduction. Furthermore, the specific expression pattern of farnesoic acid O-methyltransferase suggests that final synthesis of MF is carried out in different target tissues, where it is regulated by esterase enzymes under a tissue-specific hormonal control. Finally, the presence of a vertebrate type steroid receptor in hepatopancreas and intestine besides being highly expressed in female gonads, suggest a role of that receptor during sexual maturation.

Understanding and managing psychological disorders in patients with inflammatory bowel disease: a practical guide.

Mood disturbances such as anxiety and depression are common in patients with inflammatory bowel disease (IBD), and impact negatively on their quality of life and disease course. An integrated multidisciplinary IBD team, which includes access to psychology and psychiatry opinion, makes possible the prompt recognition and management of psychological disturbance in patients with IBD. Based on our experience and existing literature, including systematic reviews of the effectiveness of available treatment modalities, a stepwise approach to the maintenance and restoration of psychological well-being is recommended, evolving upwards from lifestyle advice, through behavioural therapies to pharmacotherapy.

Transcriptome profile in heat resilient Pacific oyster Crassostrea gigas families under thermal challenge.

Since the introduction of the Pacific oyster Crassostrea gigas in Baja California Sur, Mexico, its culture has faced environmental challenges, specifically increasing temperatures that result in high mortalities. The inter-tidal zone seawater temperature during a year at the Baja California Peninsula broadly ranges from 7 °C to 39 °C. Therefore, to understand how oysters respond to heat stress during daily temperature oscillations, heat-resistant (RR, father, and mother resistant) and heat-susceptible (SS, both parents susceptible) phenotypes families from a C. gigas breeding program were exposed to a thermal challenge. Based on a laboratory-simulated daily oscillatory thermal challenge (26 to 34 °C) for 30 days, RR phenotype presented differences compared to SS phenotype since the beginning (day 0) of the thermal challenge. Gene expression analyses revealed 1822 differentially expressed up-regulated transcripts in RR, related to functions of metabolic processes, biological regulation, and response to stimulus and signaling. At the end of the experiment (day 30), 2660 differentially expressed up-regulated transcripts were identified in RR. Functional analysis of the genes expressed indicates responses of regulation of biological processes and response to a stimulus. Additionally, 340 genes were differentially expressed among RR vs. SS from the beginning to the end of the thermal challenge, where 170 genes were up-regulated, and 170 were down-regulated. These transcriptomic profiles represent the first report to identify gene expression markers associated with RR phenotypes for the Pacific oyster to the future broodstock selection.

Multidisciplinary Perinatal Care in IBD.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] are often affected during their reproductive years and may have many perinatal queries that require the comprehensive perspectives of a multidisciplinary team [MDT]. The purpose of this topical review is to assess the scientific evidence and provide expert opinion related to nutritional, psychological and supportive care of women and their infants throughout the prenatal, antenatal and infant periods. METHODS: A consensus expert panel of a paediatrician, gastroenterologists, nurses and dietitians was convened by the European Crohn's and Colitis Organisation. This panel critically reviewed literature related to the non-medical management of patients with IBD during preconception, pregnancy, the postnatal period and the first years of the infant's life. Statements were developed using an e-Delphi process over two rounds and were confirmed when ≥80% of experts agreed with the statements. RESULTS: A total of 19 current practice positions were developed that cover the preconception period, pregnancy and lactation, and early-life exposures associated with risk of IBD. Development of the infant microbiome and its role in the immune system and topics including nutritional optimization, psychological support and education relating to early life were reviewed. CONCLUSIONS: Patients with IBD have unique nutritional and psychosocial needs that may affect fertility and pregnancy outcomes. The early-life environment of infants born to parents with IBD may be associated with subsequent development of IBD in offspring. An MDT is the optimal setting to support and counsel patients throughout the perinatal period.

Broadening Participation: 21st Century Opportunities for Amateurs in Biology Research.

The modern field of biology has its roots in the curiosity and skill of amateur researchers and has never been purely the domain of professionals. Today, professionals and amateurs contribute to biology research, working both together and independently. Well-targeted and holistic investment in amateur biology research could bring a range of benefits that, in addition to positive societal benefits, may help to address the considerable challenges facing our planet in the 21st century. We highlight how recent advances in amateur biology have been facilitated by innovations in digital infrastructure as well as the development of community biology laboratories, launched over the last decade, and we provide recommendations for how individuals can support the integration of amateurs into biology research. The benefits of investment in amateur biology research could be many-fold, however, without a clear consideration of equity, efforts to promote amateur biology could exacerbate structural inequalities around access to and benefits from STEM. The future of the field of biology relies on integrating a diversity of perspectives and approaches-amateur biology researchers have an important role to play.

Effects of 5-ALA mediated photodynamic therapy in oral cancer stem cells.

The aim of the present study was to investigate the effects of PDT using the photosensitizer 5-aminoulevulinic acid (5-ALA) in oral squamous cell carcinoma (OSCC) behavior, mainly regarding its role on the cancer stem cell (CSC) phenotypes and in maintenance of the stem cell properties. Two OSCC cell lines were used and divided in the groups: Control, 5-ALA, LED 6 J/cm2 and PDT. MTT and Neutral red assays were used to access cellular viability, cell migration was evaluated by the wound healing assay. The stem cell phenotype was analyzed by flow cytometry to evaluate the CD44high/ESAhigh, CD44high/ESAlow and CD44low populations, by the clonogenic and tumor sphere formation assays as well as by RT-qPCR. The presence of Protoporphyrin IX in each CSC fraction was evaluated by flow cytometry. The OSCC cell lines showed a significant decrease in cell viability and migration after PDT. The percentage of CD44high/ESAhigh cells decreased after PDT, which was associated with an increase in the CD44low cells and with a functional decrease in the colony and sphere formation capacity. CD44high/ESAhigh cells showed increased PpIX, which contributed for their greater sensitivity to PDT. INV gene increased significantly after PDT, indicating cellular differentiation. Altogether, our results demonstrate that 5-ALA mediated PDT decreases not only the fraction of oral CSC but also their functional capabilities, inducing their differentiation.

Photobiomodulation therapy in management of cancer therapy-induced side effects: WALT position paper 2022.

Disclaimer: This article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols. Objective: This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT). Background: There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care. Methods: A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed. Results: There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors. Conclusions: There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.

Knowledge and attitudes about influenza vaccination in rheumatic diseases patients.

Patients with rheumatic diseases (RD) have a higher risk of morbidity and mortality from vaccine-preventable infections attributed to disease activity, comorbidities, immunosuppressive therapy, and other factors. Vaccines are one of the safest and most effective public health interventions. The aim of this study was to investigate knowledge and attitudes about influenza vaccination as factors influencing vaccine uptake and hesitancy in a population with RD. A descriptive cross-sectional study was designed. A self-administered questionnaire surveyed age, RD diagnosis, ten questions about the uptake, safety and efficacy of influenza vaccine, knowledge of cost-free availability, and the relationship between influenza vaccination and RD. A total of 223 questionnaires were filled; 79.8% of patients were vaccinated for influenza at least once. Uptake by diagnosis was 80.3% in rheumatoid arthritis, 76.2% in osteoarthritis, 86.7% in lupus, 73.9% in other auto-immune diseases (AID), and 60% in other non-AID; 83.9% of patients considered influenza vaccine as safe and effective. From those who had never been vaccinated, 26.7% of patients did not consider influenza vaccine safe and effective vs. 13.5% among patients who had been vaccinated (P = .032). Only 7.6% considered that RD patients could not be vaccinated; 11.7% thought that influenza vaccine would worsen their RD symptoms. This study showed that concerns about safety, efficacy, side effects, fear of the vaccine, and knowledge of cost diminished vaccine uptake. These are factors related to confidence, complacency, and convenience as components of vaccine hesitancy that affect influenza vaccination in RD patients.

Allotriploid genotypic assignment in abalone larvae by detection of microsatellite-recombinant genotypes.

Abalone species are different from most mollusks utilized in aquaculture as they are known to hybridize in laboratory-induced matings. Allotriploidization of hybrid abalone has not yet been studied, and methodology useful in verifying the genotypic condition of such allotriploids do not exist. Genotypic verification of hybridization and allotriploidization in a cross of Haliotis fulgens and Haliotis rufescens was performed utilizing 6 crossamplifying microsatellite loci. Five H. rufescens spawns were used in this experiment, dividing each spawn into control and experimental hybrid groups and further into diploids and triploids. Two microsatellite loci developed for H. fulgens and H. rufescens allowed for the genotypic identification of hybrids within diploid and triploids. To further verify the percentage of allotriploids within the genotypic hybrids in the triploid hybrid groups, microsatellite loci originally developed in Haliotis corrugata and Haliotis kamtschatkana were tested for crossamplification in H. fulgens and H. rufescens. Of 21 loci, 4 were chosen for this study based on their crossamplification, heterozygosity in the females, and centromere recombination frequencies. Allotriploids in triploid-hybrid larvae were then detected by identifying larvae with recombinant genotypes at any of those loci. One family had low success verification associated with reduced recombination frequencies for all loci in that family. These results demonstrate that allotriploid verification at larval stages is feasible but depends on the number of loci available, their crossamplification in the species, and their recombination frequencies.

In vitro sperm storage with poultry oviductal secretions.

In the hen oviduct, tubules have been identified that preserve the sperm, maintaining viability for up to 15 weeks. This study aimed to evaluate the physiological status of rooster sperm when preserved in vitro with uterus vaginal junction secretions (UVJS). Males and females of the Rhode Island breed were used. Sperm aliquots were prepared using Lake extender and Lake extender with UVJS (10.00%, 30.00%, 60.00%, and 90.00%). Subsequently, a basic sperm evaluation was performed and sperm physiological status was determined through the presence and distribution of Ca2+ and its acrosomal reaction capability via perivitelline layer (PVL) co-incubation. It was observed that motility was decreased in sperm preserved with UVJS at 6 and 24 hr) compared to 40 min and fresh semen. The sperm decapacitation percentage was increased when preserved with UVJS at 40 min, 6 and 24 hr compared to fresh semen. The acrosomal reaction was increased in sperm co-incubated with PVL, even when preserved with UVJS. It was concluded that UVJS induced physiological changes in sperm by inducing a decapacitation process, which increased sperm viability when preserved in vitro.

Effectiveness and safety of vedolizumab in inflammatory bowel disease patients aged 60 and over: an observational multicenter UK experience.

BACKGROUND: The GEMINI trials established the efficacy of vedolizumab in moderate-to-severe inflammatory bowel disease (IBD) and demonstrated a favorable safety profile, suggesting it may be advantageous in older patients at greater risk of treatment-related complications. However, there is a paucity of data exploring the outcomes of vedolizumab in this group. Our objective was to determine the clinical effectiveness and safety of vedolizumab in older IBD patients within a real-world multicenter UK cohort. METHODS: A retrospective review of electronic records across 6 UK hospitals was undertaken to evaluate the clinical effectiveness and safety outcomes of vedolizumab in IBD patients aged ≥60 at start of therapy. Rates of clinical response, remission and corticosteroid-free remission were assessed at weeks 14 and 52, using validated clinical indices, and were compared to historical controls from real-world vedolizumab-treated cohorts unstratified by age. RESULTS: Of 74 patients aged 60 years or above (median 66 years), 48 were included in our effectiveness analysis (29 ulcerative colitis, 19 Crohn's disease). Rates of clinical response, remission and corticosteroid-free remission at week 14 were 64%, 48% and 30%, respectively. By week 52, the rates of clinical response, remission, and corticosteroid-free remission were 52%, 38%, and 32%, respectively. Six (8%) patients experienced adverse effects. Effectiveness and safety outcomes were comparable to those of age-unstratified vedolizumab-treated cohorts. CONCLUSION: Our 1-year outcome data suggests that vedolizumab is safe and effective in older IBD patients and broadly comparable to cohorts unselected by age.

Testicular development induced by GnRH-IS in budgerigar (Melopsittacus undulatus).

Nowadays, the third part of parrots in the world is endangered or vulnerable; an alternative for their preservation is assisted reproduction in captivity through hormonal manipulation. In birds, GnRH is the main hormone which controls reproductive physiology, it is known there are three types: GnRH-I, GnRH-II and GnRH-III, involved in the release or inhibition of luteinizing hormone and follicle stimulant hormone to control gonadal and gametic development. The objective of this study was, to evaluate the effect of administrating synthetic GnRH-I in the testicular development of Melopsittacus undulatus. Twenty-eight adult budgerigars were randomly divided in two groups: control (n=14) and treated (n=14) with a unique dose of synthetic GnRH-I. Testicular development was assessed through ultrasonography and density was evaluated with pixels. Germinal diameter and thickness of germinal epithelium were determined with histology; there were identified and countified different cellular strains in seminiferous tubules therefore spermatobioscopy. Results. Ecographic density was: control group: 76 ± 7 pixels, treated group 41 ± 3 pixels. Thickness of germinal epitellium, 51.5 ± 2.9µm and 73.1 ± 3.1µm, for control group and treated group respectively. Sperm concentration in the treated group was 300% superior than in control group. It is concluded that the administration of synthetic GnRH-I, is a viable alternative to be used as part of the assisted reproductive techniques to induce reproduction.

A natural antisense transcript of the fem-1 gene was found expressed in female gonads during the characterization, expression profile, and cellular localization of the fem-1 gene in Pacific white shrimp Penaeus vannamei.

The fem-1 gene in Caenorhabditis elegans is involved in sex differentiation; it is specifically required for all aspects of male development. In this study, the full-length cDNA of the fem-1 (Pvfem-1) gene was isolated from the Pacific whiteleg shrimp Penaeus vannamei. The Pvfem-1 transcript is 3778 nt long and encodes a putative protein (PvFEM-1) of 638 amino acids that presented eight ankyrin repeats. The translated protein showed a significant (P < 0.05) structural similitude by superposition with C. elegans FEM-1 protein. Pvfem-1 expression was evaluated by qPCR and in situ hybridization (ISH) during embryogenesis, larval development, and gonads of both genders in subadult and adult life stages. Pvfem-1 was found expressed in brain, intestine, hepatopancreas, and in the gonads of both genders in subadults and adults when quantified by RT-qPCR. A significant finding was the discovery of a natural antisense transcript (NAT) of Pvfem-1 by ISH. It was present in the oocyte nucleus of subadult female shrimp gonads but was not seen within oocytes from adult females, although it was detected in follicular cells, suggesting a possible post-transcriptional regulation of Pvfem-1 in female gonad. Conversely, in males, no NAT was observed, and Pvfem-1 was found expressed in spermatogonia of both, subadult and adult shrimps indicating a function in male sexual differentiation and gametes generation. This study represents the first step for future functional analysis that is expected to contribute to clarifying the role of Pvfem-1 in sex differentiation and determination.