Synthesis and evaluation of 5,15-diaryltetrabenzoporphyrins as photosensitizers for photo-diagnosis and photodynamic activity of tumors.

Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar2TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at ∼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC50 value of 0.45 µM, and phototherapeutic index of 25.8. Flow cytometry revealed that I3 could induce distinct cell apoptosis. In vivo studies revealed that compound I3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors.

Bioengineering autologous cartilage grafts for functional posterior lamellar eyelid reconstruction: A preliminary study in rabbits.

The reconstruction of posterior lamellar eyelid defects remains a significant challenge in clinical practice due to anatomical complexity, specialized function, and aesthetic concerns. The ideal substitute for the posterior lamellar should replicate the native tarsoconjunctival tissue, providing both mechanical support for the eyelids and a smooth surface for the globe after implantation. In this study, we present an innovative approach utilizing tissue-engineered cartilage (TEC) grafts generated from rabbit auricular chondrocytes and a commercialized type I collagen sponge to reconstruct critical-sized posterior lamellar defects in rabbits. The TEC grafts demonstrated remarkable mechanical strength and maintained a stable cartilaginous phenotype both in vitro and at 6 months post-implantation in immunodeficient mice. When employed as autografts to reconstruct tarsal plate defects in rabbits' upper eyelids, these TEC grafts successfully restored normal eyelid morphology, facilitated smooth eyelid movement, and preserved the histological structure of the conjunctival epithelium. When applied in bilayered tarsoconjunctival defect reconstruction, these TEC grafts not only maintained the normal contour of the upper eyelid but also supported conjunctival epithelial cell migration and growth from the defect margin towards the centre. These findings highlight that auricular chondrocyte-based TEC grafts hold great promise as potential candidates for clinical posterior lamellar reconstruction. STATEMENT OF SIGNIFICANCE: The complex structure and function of the posterior lamellar eyelid continue to be significant challenges for clinical reconstructive surgeries. In this study, we utilized autologous auricular chondrocyte-based TEC grafts for posterior lamellar eyelid reconstruction in a preclinical rabbit model. The TEC grafts exhibited native cartilaginous histomorphology and comparable mechanical strength to those of the native human tarsal plate. In rabbit models with either tarsal plate defects alone or bilayered tarsoconjunctival defects, TEC grafts successfully restored the normal eyelid contour and movement, as well as supported preservation and growth of conjunctival epithelium. This is the first study to demonstrate autologous TEC grafts can be employed for repairing tarsal plate defects, thereby offering an alternative therapeutic approach for treating posterior lamellar defects in clinic settings.

Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy.

Diabetes presents a pressing healthcare crisis, necessitating innovative solutions. Organoid technologies have rapidly advanced, leading to the emergence of bioengineering islet organoids as an unlimited source of insulin-producing cells for treating insulin-dependent diabetes. This advancement surpasses the need for cadaveric islet transplantation. However, clinical translation of this approach faces two major limitations: immature endocrine function and the absence of a perfusable vasculature compared to primary human islets. In this review, we summarize the latest developments in bioengineering functional islet organoids in vitro and promoting vascularization of organoid grafts before and after transplantation. We highlight the crucial roles of the vasculature in ensuring long-term survival, maturation, and functionality of islet organoids. Additionally, we discuss key considerations that must be addressed before clinical translation of islet organoid-based therapy, including functional immaturity, undesired heterogeneity, and potential tumorigenic risks.

Novel Perspectives on Nanotechnological and Biomedical Implications of Monotherapy or Combination Regimen of Lactoferrin.

Lactoferrin (LF) is a protein molecule with a wide variety of physiological properties. LF has broadspectrum antibacterial, antiviral, antioxidant, and antitumor, and possesses immunomodulatory properties to regulate immunity and gastrointestinal function. The main aim of this review is to explore the recent investigations on the functional role of LF against several human disorders and diseases through monotherapy or combinatorial regimens with other biological/chemotherapeutic agents through novel nanoformulations. We significantly searched public databases such as Pubmed, National Library of Medicine, relemed, Scopus and collected published reports pertaining to these recent reports on lactoferrin as a monotherapy or combination therapy, and its nanoformulations. We have discussed vividly the role of LF as a growth factor with substantial potential that can promote cell growth and regeneration potential for repairing tissues such as bone, skin, mucosa, and tendons. In addition, we have discussed novel perspectives on the role of LF as an inductive factor for the proliferation of stem cells in tissue recovery and discussed its novel modulating effects in ameliorating cancer and microbial growth through several signaling cascades via monotherapy or combinatorial regimens. Furthermore, the regeneration potential of this protein is reviewed to explore the efficacy and prospects of new treatment methods. This review benefits various microbiologists, stem cell therapists, and oncologists to explore the efficacy of LF in several segments of medicine by examining its ability as a stem cell differentiation factor, and anticancer agent or antimicrobial agent through novel formulations in preclinical or clinical study.

Feasibility test of a sapphire cryoprobe with optical monitoring of tissue freezing.

This article describes a sapphire cryoprobe as a promising solution to the significant problem of modern cryosurgery that is the monitoring of tissue freezing. This probe consists of a sapphire rod manufactured by the edge-defined film-fed growth technique from Al2 O3 melt and optical fibers accommodated inside the rod and connected to the source and the detector. The probe's design enables detection of spatially resolved diffuse reflected intensities of tissue optical response, which are used for the estimation of tissue freezing depth. The current type of the 12.5-mm diameter sapphire probe cooled down by the liquid nitrogen assumes a superficial cryoablation. The experimental test made by using a gelatin-intralipid tissue phantom shows the feasibility of such concept, revealing the capabilities of monitoring the freezing depth up to 10 mm by the particular instrumentation realization of the probe. This justifies a potential of sapphire-based instruments aided by optical diagnosis in modern cryosurgery.

Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers.

Obesity and associated chronic inflammation were shown to facilitate breast cancer (BC) growth and metastasis. Leptin, adiponectin, estrogen, and several pro-inflammatory cytokines are involved in the development of obesity-driven BC through the activation of multiple oncogenic and pro-inflammatory pathways. The aim of this study was to assess the reported mechanisms of obesity-induced breast carcinogenesis and effectiveness of conventional and complementary BC therapies. We screened published original articles, reviews, and meta-analyses that addressed the involvement of obesity-related signaling mechanisms in BC development, BC treatment/prevention approaches, and posttreatment complications. PubMed, Medline, eMedicine, National Library of Medicine (NLM), and ReleMed databases were used to retrieve relevant studies using a set of keywords, including "obesity," "oncogenic signaling pathways," "inflammation," "surgery," "radiotherapy," "conventional therapies," and "diet." Multiple studies indicated that effective BC treatment requires the involvement of diet- and exercise-based approaches in obese postmenopausal women. Furthermore, active lifestyle and diet-related interventions improved the patients' overall quality of life and minimized adverse side effects after traditional BC treatment, including postsurgical lymphedema, post-chemo nausea, vomiting, and fatigue. Further investigation of beneficial effects of diet and physical activity may help improve obesity-linked cancer therapies.

Models of head and neck squamous cell carcinoma using bioengineering approaches.

The use of bioengineering methods and approaches is extremely promising for the development of experimental models of cancer, especially head and neck squamous cell carcinomas (HNSCC) that are characterized by early metastasis and rapid progression., for testing novel anticancer drugs and diagnostics. This review summarizes the most relevant HNSCC tumor models used to this day as well as future directions for improved modeling of the malignant disease. Apart from conventional 2D-cell cultivation methods and in vivo animal cancer models a number of bioengineering techniques of modeling HNSCC tumors were reported: genetic-engineering, ethanol/tobacco exposure experiment, spheroids, hydrogel-based cell culture, scaffold-based cell culture, microfluidics, bone-tumor niche cell culture, cancer and normal cells co-culture, cancer cells, and bacteria co-culture. An organized set of these models can constitute a system of HNSCC experimental modeling, which gives potential towards developing the newest approaches in the diagnosis, prevention, and treatment of HNSCC.

A method for intra-percardial PDT for malignant mesothelioma.

We describe a case of a 35-year-old patient with recurrent non-resectable pleural mesothelioma cT4N0M0 with a confirmed malignant pericardial effusion, threatening for cardiac tamponade. We performed and described our experience of intrapericardial photodynamic therapy which was well tolerated and with a good survival result. After 12 months of follow-up our patient showed no signs of pericardial effusion and in stable condition, keeping high level of quality of life. This clinical case is an example of the excellent palliative effect of photodynamic therapy together with concomitant immunotherapy.

Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers.

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.

Study of the Therapeutic Efficiency of Transduced Olfactory Ensheathing Cells in Spinal Cord Cysts.

Posttraumatic spinal cord cysts are difficult to treat with medication and surgery. Gene-cell therapy is a promising area of treatment for such patients. However, optimal gene-cell construct for this therapy has not been developed. We investigated the therapeutic efficiency of human olfactory ensheathing cells (OECs) transduced by adenoviral vector encoding the mature form of brain-derived neurotrophic factor (mBDNF) in spinal cord cysts. The adenoviral vectors Ad5/35-CAG-mBDNF and Ad5/35-CAG-Fluc were constructed. Spinal cysts were modeled in female Wistar rats. We selected animals at the early and intermediate stages of recovery with scores to 13 according to the Basso, Beattie and Bresnahan (BBB) scale. The efficiency of therapy was evaluated by BBB tests. No cytotoxicity was detected using the Resazurin/AlamarBlue assay for both vectors at multiplicity of infection (MOIs) of 1, 5, and 25. There was an increase in the proliferation of cells treated with Ad5/35-CAG-mBDNF at MOIs of 5 and 25. The hind limb mobility after the transplantation of Ad5/35-CAG-mBDNF- and Ad5/35-CAG-Fluc-transduced human OECs and nontransduced OECs had approximately the same tendency to improve. Cyst reduction was observed with the transplantation of all the samples. Although Ad5/35-CAG-mBDNF-transduced OECs had high BDNF expression levels in vitro, these cells lacked positive effect in vivo because they did not exhibit significant effect concerning functional test when comparing the groups that received the same numbers of OECs. The therapeutic efficiency of transduced OECs appears to be due to the cell component. The autological and tissue-specific human OECs are promising for the personalized cell therapy. It is extremely important to test new gene-cell constructs based on these cells for further clinical use.

Cellular effects of terahertz waves.

SIGNIFICANCE: An increasing interest in the area of biological effects at exposure of tissues and cells to the terahertz (THz) radiation is driven by a rapid progress in THz biophotonics, observed during the past decades. Despite the attractiveness of THz technology for medical diagnosis and therapy, there is still quite limited knowledge about safe limits of THz exposure. Different modes of THz exposure of tissues and cells, including continuous-wave versus pulsed radiation, various powers, and number and duration of exposure cycles, ought to be systematically studied. AIM: We provide an overview of recent research results in the area of biological effects at exposure of tissues and cells to THz waves. APPROACH: We start with a brief overview of general features of the THz-wave-tissue interactions, as well as modern THz emitters, with an emphasis on those that are reliable for studying the biological effects of THz waves. Then, we consider three levels of biological system organization, at which the exposure effects are considered: (i) solutions of biological molecules; (ii) cultures of cells, individual cells, and cell structures; and (iii) entire organs or organisms; special attention is devoted to the cellular level. We distinguish thermal and nonthermal mechanisms of THz-wave-cell interactions and discuss a problem of adequate estimation of the THz biological effects' specificity. The problem of experimental data reproducibility, caused by rareness of the THz experimental setups and an absence of unitary protocols, is also considered. RESULTS: The summarized data demonstrate the current stage of the research activity and knowledge about the THz exposure on living objects. CONCLUSIONS: This review helps the biomedical optics community to summarize up-to-date knowledge in the area of cell exposure to THz radiation, and paves the ways for the development of THz safety standards and THz therapeutic applications.

Psychological and Aesthetic Outcomes in Breast Cancer Patients.

BACKGROUND: Patients who undergo breast cancer treatment require psychosocial and aesthetic rehabilitation. Advantages of breast reconstruction in-patient rehabilitation are well known. Oncoplastic organ-preserving surgery offers aesthetically better results, yet is often considered less safe than more radical procedures. We compared the aesthetic and psychological outcomes in patients undergoing breast reconstruction and oncoplastic breast cancer treatment. METHODS: In total, 1130 patients who received either breast reconstruction or oncoplastic breast cancer surgery were included in the study. Patients were classified into two groups. Group 1 included 510 patients who received breast reconstruction surgery. Group 2 included 620 patients who received oncoplastic surgery. The following aspects were compared between the two groups: demographics, tumor progression, and immunohistochemical aspects, complications, hospitalization stay, and psychological and aesthetic outcomes. RESULTS: Patients in the oncoplastic group showed statistically significant higher psychosocial and aesthetic outcomes, as well as lower incidence of complications, revision rate, disease progression, and recurrence. The majority of oncoplastic patients were treated in early stages of breast cancer. CONCLUSION: Offering superior treatment results, oncoplastic organ-preserving surgery should be favored in patients with earlier stages of cancer progression.

Efficacy of da Vinci robot-assisted lymph node surgery than conventional axillary lymph node dissection in breast cancer - A comparative study.

BACKGROUND: da Vinci robot-assisted axillary lymph node dissection (dVALND) can be a minimally invasive technique to minimize post-operative complications. OBJECTIVE: To explore the clinical efficacy of dVALND in breast cancer (BC) patients for mitigating the postoperative complications than conventional ALND. METHODS: Total 60 female patients with BC were admitted to our hospitals since September 2018, and these patients segregated into two groups of 30 patients each. Modified radical mastectomy for BC was performed to the patients in both groups. In Group 1 (control group), ALND was performed using conventional mode of axillary lymph node surgery. In Group 2 (Test group), the dVALND was performed using da Vinci robot-assisted surgery. Wound healing, aesthetic effect and patient's satisfaction were evaluated after conventional method and dVALND. RESULTS: Postoperative complications viz., wound infection (1/30 (3.33%), p < 0.05), fat necrosis (3/30 (10%), p < 0.05) and lymphedema of upper limbs (2/30 (6.67%), p < 0.05) were observed in dVALND than conventional surgery. Local recurrence or metastasis was minimized and overall aesthetic effect not observed during follow-up. CONCLUSION: dVALND improved the overall patient's quality of life by mitigating postoperative complications than ALND.

Special Section Guest Editorial: Advances in Terahertz Biomedical Science and Applications.

The editorial introduces a special section of the Journal of Biomedical Optics on Advances in Terahertz Biomedical Science and Applications. This special section includes one review and ten research papers addressing the complex challenges of terahertz biophotonics and related areas of biomedical optics.

Lactoferrin as a regenerative agent: The old-new panacea?

Lactoferrin (Lf) possesses various biological properties and therapeutic potentials being a perspective anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, and immunomodulatory agent. A significant body of literature has also demonstrated that Lf modulates regenerative processes in different anatomical structures, such as bone, cartilage, skin, mucosa, cornea, tendon, vasculature, and adipose tissue. Hence, this review collected and analyzed the data on the regenerative effects of Lf, as well as paid specific attention to their molecular basis. Furthermore, tissue and condition-specific activities of different Lf types as well as problems of their delivery to the targeted organs were discussed. The authors strongly hope that this review will stimulate researchers to focus on the highlighted topics thus accelerating the progress of Lf's wider clinical application.

Botulinum Toxin Type A as a Tool for Correcting Capsular Contracture after Reconstructive Breast Surgery.

Capsular contracture is one of the most common complications after breast reconstruction. Surgical treatment is the main option for capsular contracture correction and includes capsulotomy, capsulectomy, and removal/replacement of the affected implant. However, the surgical trauma from reoperation, along with reduced quality of life, in patients with clinically significant capsular contracture has prompted a search for alternative treatment options. The use of the botulinum toxin type A in the treatment of neurological diseases and of keloid scars in aesthetic practice nudged the idea of using the same toxin for the correction of capsular contractures in breast cancer patients. Botulinum toxin type A injection is an easy procedure requiring no anesthesia or inpatient care. The treatment has few side effects. In addition, the injection does not cause sensory loss or dysesthesia. We described a clinical case of the capsular contracture correction using incobotulinumtoxin A. Capsular contracture IV developed 4 months post surgery after long-term lymphorrhea. Radiation therapy was not performed. According to the internal protocol, the patient was advised to undergo incobotulinumtoxin A treatment instead of surgery. Within 1 week after the second injection, all symptoms decreased-specifically, the general shape of the reconstructed breast. Also, the pain syndrome disappeared.

Therapeutic Potential of Mesenchymal Stem Cells for Postmastectomy Lymphedema: A Literature Review.

Upper limb lymphedema is one of the most common complications after breast cancer surgery and radiotherapy. Despite various physical therapy and surgical options available, the impaired lymph fluid drainage may be progressive due to lymphatic vascular insufficiency making treatment more difficulty. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases. The wide applicability of cell therapy has been reviewed throughout literature. This review provides an overview of recent progress in the therapeutic effect of adult stem cells for primary and secondary lymphedema after breast surgery in preclinical studies and clinical cases. We start with a brief introduction about the pathophysiological mechanisms of postmastectomy lymphedema. Regarding existing treatments, we systematically summarize the benefits and limitations of recent progress. Because of their multidirectional differentiation potential and growth factor secretion, stem cell therapy shows promising results in the management of light to severe lymphedema. Increasing evidences have demonstrated a noticeable reduction in postmastectomy lymphedema and increased lymph-angiogenesis after specific stem cell therapy. Current data suggests that stem cell therapy in lymphedema treatment provides reversal of pathological reorganization associated with lymphedema progression. Finally, we propose potential strategies for overcoming the challenges in the development of multipotent progenitor cells for the treatment and prevention of lymphedema in clinical practice.

Microfocusing sapphire capillary needle for laser surgery and therapy: Fabrication and characterization.

A sapphire shaped capillary needle designed for collimating and focusing of laser radiation was proposed and fabricated by the edge-defined film-fed growth technique. It features an as-grown surface quality, high transparency for visible and near-infrared radiation, high thermal and chemical resistance and the complex shape of the tip, which protects silica fibers. The needle's geometrical parameters can be adjusted for use in various situations, such as type of tissue, modality of therapy and treatment protocol. The focusing effect was demonstrated numerically and observed experimentally during coagulation of the ex vivo porcine liver samples. This needle in combination with 0.22NA optical fiber allows intensive and uniform coagulation of 150 mm3 volume interstitially and 30 mm3 superficially by laser exposure with 280 J without tissue carbonization and fiber damaging along with delicate treatment of small areas. The demonstrated results reveal the perspectives of the proposed sapphire microfocusing needle for laser surgery and therapy.