Expanded substrate specificity supported by P1' and P2' residues enables bacterial dipeptidyl-peptidase 7 to degrade bioactive peptides.

Dipeptide production from extracellular proteins is crucial for Porphyromonas gingivalis, a pathogen related to chronic periodontitis, because its energy production is entirely dependent on the metabolism of amino acids predominantly incorporated as dipeptides. These dipeptides are produced by periplasmic dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11. Although the substrate specificities of these four DPPs cover most amino acids at the penultimate position from the N terminus (P1), no DPP is known to cleave penultimate Gly, Ser, Thr, or His. Here, we report an expanded substrate preference of bacterial DPP7 that covers those residues. MALDI-TOF mass spectrometry analysis demonstrated that DPP7 efficiently degraded incretins and other gastrointestinal peptides, which were successively cleaved at every second residue, including Ala, Gly, Ser, and Gln, as well as authentic hydrophobic residues. Intravenous injection of DPP7 into mice orally administered glucose caused declines in plasma glucagon-like peptide-1 and insulin, accompanied by increased blood glucose levels. A newly developed coupled enzyme reaction system that uses synthetic fluorogenic peptides revealed that the P1' and P2' residues of substrates significantly elevated kcat values, providing an expanded substrate preference. This activity enhancement was most effective toward the substrates with nonfavorable but nonrepulsive P1 residues in DPP7. Enhancement of kcat by prime-side residues was also observed in DPP11 but not DPP4 and DPP5. Based on this expanded substrate specificity, we demonstrate that a combination of DPPs enables proteolytic liberation of all types of N-terminal dipeptides and ensures P. gingivalis growth and pathogenicity.

Are foundation doctors equipped with the skills necessary for the assessment and referral of a patient presenting with a suspected facial skin malignancy?

BACKGROUND: The incidence of skin cancer (SC) has increased in recent years with it being the most common cancer within the UK. The management of SC requires a multidisciplinary approach involving dermatologists and surgical specialities. OBJECTIVES: To assess the confidence of current foundation trainees (FTs) in the assessment of facial SC and referral for surgical management and reconstruction. METHODS: An online survey was distributed via social media and completed by 142 FTs across 13 deaneries. Two higher training respondents were excluded. RESULTS: We found that 50% (71/142) of trainees had only examined one or two patients with SC and 25.3% (36/142) had no experience in SC assessment. Most FTs were not confident in performing a full skin examination (90.2%, 119/132), formulating differential diagnoses for a pigmented facial lesion (45.3%, 64/141) or investigating a facial SC (87.9%, 124/141). Facial defects requiring reconstruction (87.3%, 124/142) were more likely to be referred to plastic surgery. CONCLUSIONS: FTs were not confident in performing full skin examinations nor formulating diagnoses for pigmented lesions. This is concerning given that the majority of FTs will enter general practice and therefore exposure to SC will be common. This may in turn place greater burden on secondary care services such as dermatology and allied surgical specialities resulting in a greater caseload in an already stretched service in the UK. The integration of the British Association of Dermatology undergraduate syllabus into the medical school curriculum should improve confidence in the detection and management of SC at both undergraduate and postgraduate levels.

SARS-CoV-2 infection pattern, transmission and treatment: Multi-center study in low to middle-income districts hospitals in Punjab, Pakistan.

Pakistan has reported a substantial number of COVID-19 cases since 2020. A multicenter observational study was conducted to identify the pattern of SARS-CoV-2 infection, transmission, and treatment in patients admitted to seven low to middle-income district hospitals in the Province of Punjab, Pakistan from March to June 2020. A total of 102 patients were recruited. 57 patients tested positive and 45 developed moderate-severe COVID-19 disease. About 67% of the patients in March-April and 93% in May-June have contracted the disease from the local transmission. The mean number of symptoms in SARS-CoV-2 positive patients was significantly higher than suspected patients (6.46 vs 5.04, p=0.003). The number of deaths was low (n=8) with 86% recovery rate. Mild COVID patients received acetaminophen (n=102), azithromycin (n=8), and hydroxychloroquine (n=4) in addition to standard medical care. The treatment provided to moderate-severe cases included acetaminophen (45/45), azithromycin (45/45), Ivermectin (14/45) and corticosteroids (13/45). The mean number of antimicrobials was significantly higher in moderate-severe patients than mild cases (1.80 vs 1.12, p=0.001). Low number of deaths with a high recovery rate was reported. Diabetes was the most common comorbid condition followed by hypertension. Many antimicrobials were prescribed in both mild and moderate-severe cases that require careful review.

Characterization of substrate specificity and novel autoprocessing mechanism of dipeptidase A from Prevotella intermedia.

Prevotella intermedia, a Gram-negative anaerobic rod, is frequently observed in subgingival polymicrobial biofilms from adults with chronic periodontitis. Peptidases in periodontopathic bacteria are considered to function as etiological reagents. Prevotella intermedia OMA14 cells abundantly express an unidentified cysteine peptidase specific for Arg-4-methycoumaryl-7-amide (MCA). BAU17746 (locus tag, PIOMA14_I_1238) and BAU18827 (locus tag, PIOMA14_II_0322) emerged as candidates of this peptidase from the substrate specificity and sequence similarity with C69-family Streptococcus gordonii Arg-aminopeptidase. The recombinant form of the former solely exhibited hydrolyzing activity toward Arg-MCA, and BAU17746 possesses a 26.6% amino acid identity with the C69-family Lactobacillus helveticus dipeptidase A. It was found that BAU17746 as well as L. helveticus dipeptidase A was a P1-position Arg-specific dipeptidase A, although the L. helveticus entity, a representative of the C69 family, had been reported to be specific for Leu and Phe. The full-length form of BAU17746 was intramolecularly processed to a mature form carrying the N-terminus of Cys15. In conclusion, the marked Arg-MCA-hydrolyzing activity in Pre. intermedia was mediated by BAU17746 belonging to the C69-family dipeptidase A, in which the mature form carries an essential cysteine at the N-terminus.

Balancing the scales of safety: the criminal law's impact on patient safety and error reduction.

The chance of death from medical error within the hospital setting is 33,000 times greater than dying in an aircraft crash. Despite patient safety being central to healthcare delivery across the world, medical errors and patient harm remain prevalent. This review evaluates the role of the criminal law in regulating healthcare across England and Wales, using prior legal case studies, and focussing on the offence of gross negligence manslaughter (GNM). It further examines the extent to which the law promotes patient safety and minimises fatal errors in healthcare. Medical negligence resulting in a patient's death invokes the more punitive criminal law. In the context of the legal framework in England and Wales, individuals, including medical professionals, who are found to have caused a fatality due to 'gross negligence' may potentially be subject to manslaughter charges. Healthcare delivery is complex as it involves working in high-risk environments, invariably as part of a team. When things go wrong, it is rarely the result of an individual's error but rather a systemic failure. Human factors that may contribute to GNM include organisational influences such as trust targets and pressures to deliver results, unsafe supervision, or inadequate staffing, and preconditions for unsafe acts whereby clinicians are fatigued whilst performing multiple roles simultaneously. A more just culture is warranted in response to the criminalisation of cases of healthcare malpractice, in particular those involving GNM, in which healthcare professionals would be able to learn without fear of retribution.

The Reconstruction of Mandible Defects in War Injuries: Systematic Review and Meta-Analysis.

Study Design: Systematic Review and Meta-Analysis. Objective: There has been an increasing trend in maxillofacial injuries associated with combat trauma. Within the maxillofacial complex, the mandible is the most likely structure to be damaged during combat. The structural deficits as a result can be reconstructed with many options. These include vascularised bone grafts (VBGs), non-vascularised bone grafts (NVBGs), alloplastic implants, reconstruction bars and distraction osteogenesis. This study aimed to determine the common modality and efficacy of mandibular reconstruction in combat trauma-related defects. Methods: A literature search was conducted on Pubmed, Prospero, Dynamed, DARE, EMBASE, COCHRANE and BMJ databases. Results: A total of six articles met the inclusion criteria identifying 165 patients requiring mandibular reconstruction. Non-vascularised iliac bone graft (n = 137) was the most common method followed by ileac crest bone chips harvest using Dacron urethran osteomesh tray (n = 24) and frontoparietal grafts (n = 4). Meta-analysis of five out of six trials demonstrated an overall success rate of 85% (95% CI 79-90; I2 = 59%). A total of 13% (n = 22) of reconstructions failed either completely or partially and 21% (n = 34) of patients suffered postoperative complications. Conclusions: NVBGs are a practical, cost-effective and favourable method of war zone management of mandibular defects with success rates comparable to those reported in the civilian literature. However, general trauma principles take precedence to rule out life-threatening injuries. Due consideration of patient factors, surgical factors, and available resources are required in the first-line management of combat-related mandibular defects.

Use of human acellular dermal matrix in rhinoplasty: a systematic review of the literature and meta-analysis.

Alloplastic implants such as acellular dermal matrix (ADM) have been used for various aesthetic and reconstructive purposes since the 1990s. Rhinoplasty addresses both aesthetic and functional nasal impairments, often involving the adoption of grafting materials. Currently, autologous grafts, such as those using septal cartilage, are the gold standard. However, they pose the risk of donor site morbidity, technical challenges, and additional operative time. We review total complications, resorption/re-operation and success rates associated with the use of ADM in rhinoplasty. A literature search was conducted on PubMed, Prospero, DynaMed, DARE, EMBASE and COCHRANE databases. (Registry: CRD42023428019). A total of 462 patients from 15 studies were included, the mean (range) age was 30 (12-65) years, with a female-to-male ratio of 2:1. The most common indications for ADM were for cosmetic (35%, n = 163) and functional rhinoplasty (5%, n = 24). The most common type of ADM used was Alloderm (46%, n = 211). The most common indication for ADM was dorsal nasal augmentation (68%, n = 314). Eleven patients (2%) required revision surgery. The pooled success of ADM in rhinoplasty was 96% (95% CI 94 to 99, p = 0.93; I2 = 0%). 2% of patients developed postoperative complications and no statistically significant difference was seen in complications or success rates when comparing the different types of ADM. ADM in rhinoplasty was associated with fewer complications and re-operation rates, and similar if not less resorption compared to traditional autografts. Therefore, it can be a viable alternative to current autologous grafts in rhinoplasty surgery.

Use of autogenous fascia lata slings in the surgical correction of ptosis: a systematic review of the literature and meta-analysis.

Ptosis is an abnormally low-positioned upper eyelid. Management depends on severity, aetiology, and function of the levator palpebrae superioris muscle (LPS). This review evaluates the success of autogenous fascia lata slings (AFLS) in the surgical management of ptosis, together with complication and reoperation/revision rates. A literature search was conducted on PubMed, Google Scholar PROSPERO, Dynamed, DARE, EMBASE, Cochrane, and BMJ databases (PROSPERO registration: CRD42023475090), and 30 studies (3690 patients and 5059 eyes) were included. The average age of the patients was 14.2 years with a ratio of male:female patients of 1:0.7. A total of 2532 eyes had undergone a fascial sling with autogenous fascia lata. The average follow-up period was 32.6 months. Improvement in the margin to reflex distance 1 (MRD1) with fascial sling surgery was 2.79 mm. The rate of complications from surgery involving autogenous fascia lata was 21.3%. The most common complications included lagophthalmos (19.8%), residual ptosis (11.5%), and corneal damage (10.4%). The reoperation rate was 13.4%. Most common indications for reoperation were cosmetic, with asymmetry (18%), lid crease abnormalities (30%), and upper eyelid trimming (18%). The overall complication rate in AFLS patients was 20% (95% CI: 6 to 35, p < 0.01; I2 = 89%) versus 27% (95% CI: 14 to 40, p < 0.01; I2 = 90%) in non-AFLS patients. AFLSs are prudent in the surgical management of ptosis. The results of this review demonstrate that their use is associated with similar complication rates but fewer reoperations than other traditional techniques.

Use of supermicrosurgery in craniofacial and head and neck soft tissue reconstruction: a systematic review of the literature and meta-analysis.

Supermicrosurgery is an evolving approach in the reconstruction of head and neck (HN) and craniofacial (CF) defects. This systematic review aims to evaluate the use of supermicrosurgery for arterial or combined arterial and venous anastomoses in the reconstruction of HN and CF soft tissue defects, and the associated success, total complication, and reoperation rates. A literature search was conducted on PubMed, Dynamed, DARE, EMBASE, Cochrane, and British Medical Journal (BMJ) electronic databases (PROSPERO ID: CRD42023476825). Nine studies fulfilled the inclusion criteria with 35 patients who underwent soft tissue reconstructive procedures using supermicrosurgery. Twenty-one flaps were performed on 20 patients (57.1%) with the remaining 15 patients (42.9%) undergoing supermicrosurgical replantation. The most common pathology requiring reconstruction was HN trauma (n = 16, 45.7%) followed by malignancy (n = 15, 42.9%). The pooled success rate for supermicrosurgery was 98% (95% CI 90 to 100, p = 1.00; I2 = 0%). The cumulative complication rate across all the studies was 46% (95% CI 13 to 80, p < 0.01; I2 = 0%), and the pooled rate of reoperation was 1% (95% CI 0 to 8, p = 0.23; I2 = 24%). The use of supermicrosurgery for HN and CF soft tissue reconstruction has an overall success rate of 98%, which is commensurate with traditional microsurgery for HN reconstruction. Complication and reoperation rates are comparable to previous literature. This study confirms the feasibility of supermicrosurgery as a safe and reliable reconstructive option for HN and CF defects.

Use of scapular tip flaps in the reconstruction of head and neck defects: a systematic review and meta-analysis.

Scapular tip flaps (STF) may be used as an alternative to traditional methods of reconstruction of head and neck cancer (HNC) defects. This study aimed to establish the success and complication rates for STF in HNC reconstruction. A literature search was conducted on PubMed, BMJ Journals, DARE, EMBASE databases and Cochrane (CENTRAL) register. (Registry CRD42023428012). A total of 23 studies fulfilled the inclusion criteria with 474 patients who underwent reconstructive procedures using the STF. 100% of STF used were free flaps (STFFs). The most common reason for reconstruction was following malignancy (81.4%, n = 386). The pooled success rates in all studies using scapular tip flaps in head and neck reconstruction was 99% (95% CI, 97 to 100, p = 1.00; I2 = 0). Pooled total complication rates were 38% (95% CI, 25 to 51, p < 0.01; I2 = 90%). 19.6% required return to theatre with only 1.5% being for repeat flap coverage. The STF demonstrated an overall success rate of 99%. This is higher than other documented success rates with mainstay flaps for HNC defect reconstruction. Complication and re-operation rates were also like recorded rates. This review demonstrates the advantage of STF as a safe and versatile reconstructive option for HNC related defects. Evaluation of the literature is limited by poor-quality studies and comparability bias.

Pushing the Boundaries of Scientific Research with the use of Artificial Intelligence tools: Navigating Risks and Unleashing Possibilities.

The language of science is communicated through various modes, such as lectures, informal discussions, conferences, and peer-reviewed publications. Artificial Intelligence (AI) based writing tools, like ChatGPT, have recently become increasingly popular due to natural language processing technology advancements. ChatGPT is an AI language model that can generate text close to human writing, making it suitable for tasks such as summarizing literature, composing essays, and producing statistical studies. This technology has the potential to transform scientific communication, but concerns have been raised about its impact on the integrity of research and the role of human researchers. While this technology has advantages such as accelerating the innovation process and enhancing diversity in scientific viewpoints, it is important for the scientific community to debate and envision the consequences of its use. Publishers are working to develop guidelines for its application, which may be capable of future activities such as experiment design and peer review. As we enter the early stages of the AI revolution, it is imperative that the scientific community engages in discourse and contemplate the potential outcomes of this potentially transformative technology. With this in mind, we have outlined relevant topics as a starting point for discussion.

Mental health screening in facial cosmetic surgery: a narrative review of the literature.

The popularity of cosmetic surgery is on the increase with the face being one of the most common anatomical areas operated on. Pre-existing mental health conditions can be associated with adverse patient outcomes after cosmetic surgery and can result in deterioration of postoperative mental health and lack of patient satisfaction. Therefore, identifying the presence of psychiatric disorders through preoperative screening should be considered during consultation for facial cosmetic surgery. In this study, we reviewed the types of preoperative mental health screening tools used in cosmetic facial surgery and the prevalence of mental health conditions among patients undergoing cosmetic facial surgery. A literature search was conducted on Pubmed, Prospero, Dynamed, DARE, EMBASE, and COCHRANE databases. A total of 12 articles fulfilled the inclusion criteria. A total of 2194 participants were included in this review. Rhinoplasty (n=1154), blepharoplasty (n=138) and rhytidectomy (n=83) were the most performed facial cosmetic procedures, respectively. A total of 758 (34.1%) had a diagnosis of a potential mental health problem following the preoperative screening. With body dysmorphic disorder (BDD) being the most common (20.0%). The BDD questionnaire was the most used screening tool (n=4). Mental health diagnoses were more common in patients in low-income countries (48.4%) compared to patients from non-low-income countries (25.7%). Given our findings, we propose the routine use of mental health screening tools in all patients undergoing facial cosmetic surgery. This will improve satisfaction rates post-facial cosmetic surgery and may reduce the number of unnecessary procedures.

Use of biomaterials in the reconstruction of posterior lamellar eyelid defects: a systematic review and meta-analysis.

Eyelid defects can occur secondary to tumours, trauma, burns, and congenital factors. Among the most challenging aspects of eyelid reconstruction is the rebuilding of a tarsal substitute due to its delicate and multi-layered tissue composition. Attempts to use biomaterials for posterior lamellar reconstruction are intended to provide an alternative to traditional autograft reconstructions. In this review, we aimed to assess the types of biomaterials used for the reconstruction of the posterior lamella associated with eyelid defects and the associated clinical outcomes. A literature search was conducted on Pubmed, Prospero, Dynamed, DARE, EMBASE, and COCHRANE databases. A total of 15 articles fulfilled the inclusion criteria, and 129 patients with 142 eyelids reconstructed, using artificial grafts, were included in the review. Acellular dermis allograft (AlloDerm®, LifeCell) (n = 49) was the most common artificial graft used. A meta-analysis was performed, which demonstrated a pooled success rate of artificial grafts of 99% (95% CI 96-100, p = 0.05; I2 = 40%, total complications seen 39% (95% CI 96-100, p = 0.05; I2 = 40%) and re-operation rates of 5.6% (n = 8). The biomaterials used demonstrated an overall success rate of 99%, which is similar if not greater than that reported with the use of traditional autograft reconstruction techniques, with similar complications and fewer re-operations than autografts. This suggests that clinicians should consider the clinical use of artificial grafts for posterior lamellar reconstruction.

Can we support second degree students by incorporating non-surgical facial aesthetics into undergraduate dentistry during the first degree?

Non-surgical facial aesthetics (NSFA) are cosmetic procedures intended to reduce signs of ageing and provide facial rejuvenation. There is currently no recommendation for NSFA to be included in the undergraduate dental curriculum globally. This study aims to gain the views of final year dental students about pursuing a career in NSFA. An online survey was completed by 114 final year dental students across two English Universities. A total of 67% (77/114) of students would pursue a career in NSFA. A total of 76% (87/114) and 75% (86/114) of students were not aware of the complications associated with the administration of dermal fillers and Botox injections, respectively. Most students considered NSFA upon graduation. NSFA provides a transferable skillset and useful anatomical knowledge. Incorporation of NSFA in undergraduate education could financially support oral and maxillofacial surgery (OMFS) trainees within their second degree. This may in turn promote retention within the speciality with high financial costs associated with OMFS training.

What are the concerns of second-degree medical students entering specialty OMFS training?

Oral and maxillofacial surgery (OMFS) applicants are faced with numerous challenges. Previous research has demonstrated that financial burden, length of OMFS training, and impact on personal life are cited as major drawbacks to pursuing the specialty, with trainees having concerns about the Membership of the Royal College of Surgeons (MRCS) examinations. The current study aimed to explore second-degree medical students' concerns about obtaining a specialty training post in OMFS. An online survey was distributed via social media to second-degree students across the United Kingdom and 106 responses were received. A lack of publications and lack of involvement in research (54%) as well as attaining accreditation with the Royal College of Surgeons (27%) were cited as the primary and secondary concerns in relation to securing a higher training post. Seventy-five per cent of respondents had no first-author publications, 93% expressed concerns about passing the MRCS examination, and 73% had more than 40 OMFS procedures within their logbook. Second-degree medical students reported having ample clinical and operative experience in OMFS. Their main concerns were about research and MRCS examinations. To alleviate these concerns, BAOMS could provide educational initiatives and dedicated mentorship programmes for second-degree students, and could adopt a collaborative approach with discussion with major postgraduate training stakeholders.

Reconstruction of head and neck oncological soft tissue defects post-resection using robotic surgery: a systematic review of the current literature.

Head and neck cancer (HNC) resection often leaves soft tissue defects and exposure of vital structures. In recent years, there has been an increase in the use of robotic surgery for HNC resections. This allows for achieving smaller defects by using a tissue-sparing approach. However, this poses a challenge for reconstruction with less space available to perform microsurgery. We reviewed the efficacy of robotic surgery in the reconstruction of HNC defects by assessing the impact on flap success and complication rates. A literature search was conducted on Pubmed, Prospero, Dynamed, DARE, EMBASE, and COCHRANE databases. A total of 14 articles fulfilled the inclusion criteria with 96 patients aged mean (range) 60.7 (29-87) years, undergoing robotic reconstruction. The radial forearm flap was the most commonly used flap for robot-assisted reconstruction (n = 47). Robotic graft inset was performed in 94 cases and robotic assisted microvascular anastomoses for 25 vessels. One hundred per cent of flaps survived with a total of 25 (26.0%) complications (wound healing (n = 7), fistula formation (n = 2), haematoma (n = 4), dehiscence (n = 10), and wound infection (n = 2). Seven (12.2%) patients required additional surgery for managing complications and revision of the flap. Fewer complications were seen in patients undergoing robotic-assisted microvascular anastomoses compared with open anastomoses (4.0% versus 34.2%, p < 0.05). Robot-assisted reconstruction in HNC defects demonstrates 100% success rate with minor associated complications. Our results also support feasibility in both flap inset and microvascular anastomoses. Our results also demonstrate feasibility in both flap inset and microvascular anastomoses. Significantly fewer complications were seen with robotic-assisted microvascular anastomoses compared with open anastomoses.

Exploring the concerns of second-degree dental students on entering specialist OMFS training and their attitudes towards the second-degree curriculum.

Within the UK, oral and maxillofacial surgery (OMFS) is a competitive specialty with a rigorous training programme that currently requires dual degrees in both medicine and dentistry. Training in OMFS can present various challenges in terms of finances, length of training, and work-life balance. The current study explores the concerns of second-degree dental students in trying to obtain an OMFS specialty training post, as well as their views on the second-degree curriculum. An online survey was distributed via social media to second-degree dental students across the UK and 51 responses were received. Respondents cited a lack of publications (29%), specialty interviews (29%), and the OMFS logbook (29%) as the primary concerns about securing a higher training post. Eighty-eight per cent felt there were elements of repetition within the second degree for which competencies had already been achieved, and 88% agreed with streamlining the curriculum within the second degree. We propose that the second degree should incorporate ways to build the OMFS ST1/ST3 portfolio as part of a tailored curriculum, removing or condensing the repetitive elements, and instead emphasising areas of concern for trainees such as research, operative experience, and interview guidance. Second-degree students should be provided with mentors with an interest in research and academia to provide guidance and promote early interest in academia.

Malignant Middle Cerebral Artery Infarct Caused by Eagle's Syndrome.

Eagle's syndrome is characterised by elongation of the styloid process. The elongated styloid process can cause symptoms like dysphagia, facial or neck pain, syncope, visual changes, etc. In severe cases, it may cause a rupture or dissection of the carotid artery, which can lead to intracranial thrombo-embolism and ischemic stroke. We report a case of a 57-year-old male presenting with dysarthria and mild left-sided body weakness. An initial non-contrast computed tomography (CT) scan showed a possible right internal carotid artery thrombus. He developed worsening left-sided weakness and gaze palsy one day after the admission. Repeated CT brain and intracranial angiography were arranged, which showed significant oedema with mass effect and right internal carotid artery dissection with thrombus. He underwent decompressive craniectomy. An enlarged styloid process measuring 4.53 cm in close proximity to the cervical vasculature was also noted. He was not deemed an appropriate candidate for styloidectomy. Due to residual left-sided weakness, he had to take early retirement. He underwent extensive rehabilitation and was able to mobilize with the help of a quad stick after a period of nine months. At the five-year follow-up, there were no characteristic symptoms of Eagle's syndrome and he was mobilizing without support.

Synthesized bioactive lignin nanoparticles/polycaprolactone nanofibers: A novel nanobiocomposite for bone tissue engineering.

The use of artificial biomaterial with enhanced bioactivity for osteostimulation is a major research concern at present days. In this research, antibacterial and osteostimulative core-shell lignin nanoparticles (LgNP) were synthesized from alkali lignin using tetrahydrofuran (THF) as solvent via a simultaneous pH and solvent shifting technology. Later, LgNP-loaded polycaprolactone (PCL) composite nanofibers were fabricated via the electrospinning technique. The addition of LgNP significantly increased the diameter of the nanofibers, ranging from 400 to 2200 nm. The addition of LgNP reduced the mechanical performance, crystallinity, and porosity of the nanofibers while improving surface wetting and swelling properties of the inherently hydrophobic PCL polymer. The prepared nanofibers showed excellent bactericidal efficacy against major bone infectious Gram-positive Staphylococcus aureus bacterial strains. The incorporation of LgNP imparted superior antioxidant activity and boosted the biodegradation process of the nanofibers. The deposition of biomineral apatite with platelet-like clustered protrusions having a Ca/P ratio of 1.67 was observed while incubating the scaffold in simulated body fluid. Based on the results of the LDH and WST-1 assay, it was demonstrated that the composite nanofibers are non-toxic to pre-osteoblastic cell line (MC3T3-E1) when they are placed in direct contact with the LgNP/PCL scaffold nanofibers. The MC3T3-E1 cells exhibited excellent proliferation and attachment on the prepared composite scaffold via filopodial and lamellipodial expansion with cell-secreted Ca deposition. According to the alkaline phosphatase activity test, LgNP/PCL nanofiber scaffolds significantly improved osteogenic differentiation of MC3T3-E1 cells compared to neat PCL nanofibers. Overall, our findings suggest that LgNP/PCL nanofiber scaffold could be a promising functional biomaterial for bone tissue engineering.

Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts.

Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.