A Critical Review on the Role of Probiotics in Lung Cancer Biology and Prognosis.

Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.

Nanodelivery systems: An efficient and target-specific approach for drug-resistant cancers.

BACKGROUND: Cancer treatment is still a global health challenge. Nowadays, chemotherapy is widely applied for treating cancer and reducing its burden. However, its application might be in accordance with various adverse effects by exposing the healthy tissues and multidrug resistance (MDR), leading to disease relapse or metastasis. In addition, due to tumor heterogeneity and the varied pharmacokinetic features of prescribed drugs, combination therapy has only shown modestly improved results in MDR malignancies. Nanotechnology has been explored as a potential tool for cancer treatment, due to the efficiency of nanoparticles to function as a vehicle for drug delivery. METHODS: With this viewpoint, functionalized nanosystems have been investigated as a potential strategy to overcome drug resistance. RESULTS: This approach aims to improve the efficacy of anticancer medicines while decreasing their associated side effects through a range of mechanisms, such as bypassing drug efflux, controlling drug release, and disrupting metabolism. This review discusses the MDR mechanisms contributing to therapeutic failure, the most cutting-edge approaches used in nanomedicine to create and assess nanocarriers, and designed nanomedicine to counteract MDR with emphasis on recent developments, their potential, and limitations. CONCLUSIONS: Studies have shown that nanoparticle-mediated drug delivery confers distinct benefits over traditional pharmaceuticals, including improved biocompatibility, stability, permeability, retention effect, and targeting capabilities.

Giant Cell Tumor of Thumb Proximal Phalanx-A Case Report.

Introduction: The prevalence of giant cell tumor (GCT) of bone is approximately 5% of all primary osseous tumors. It accounts for <2% of the total cases as far as the involvement of the hand is concerned. Numerous studies stated that <1% of cases have phalangeal involvement of the thumb. Case Report: This case is delineated for its unusual location (thumb proximal phalanx) in a 42-year-old male patient managed by single-stage en-bloc excision, arthrodesis, and web-space deepening procedure without donor-site morbidity. It is known for its notorious nature for reoccurrence (10-50%) and transformation into malignancy (10%); therefore, meticulous dissection is a prerequisite. Conclusion: GCT of the thumb proximal phalanx is quite an unusual presentation. Although very rare, it is thought to be one of the most aggressive varieties of benign bone tumor observed to date. Amid a high rate of recurrence, careful preoperative planning is pivotal for fruitful outcome both anatomically and functionally.

A narrative review on the role of magnesium in immune regulation, inflammation, infectious diseases, and cancer.

BACKGROUND: Magnesium (Mg) has gained much importance recently because of its unique range of biological functions. It is one of the most significant micronutrients in biological systems. This review aims to outline the immune-regulating actions of Mg and its crucial role in regulating inflammation and immune response to infectious agents and malignancies. METHODS: We conducted a literature review on MEDLINE, PubMed, EMBASE, Web of Science to determine the impact of Mg on immune regulation in three settings of inflammation, infection, and cancer. We thoroughly examined all abstracts and full-text articles and selected the most relevant ones for inclusion in this review. RESULTS: Mg has long been associated with immunological responses, both nonspecific and specific. It plays a pivotal role in diverse immune responses by participating in multiple mechanisms. It facilitates substance P binding to lymphoblasts, promotes T helper, B cell, and macrophage responses to lymphokines, and facilitates antibody-dependent cytolysis and immune cell adherence. Besides, Mg serves as a cofactor for C'3 convertase and immunoglobulin synthesis. It additionally boasts a significant anti-cancer effect. Chronic Mg deficiency leads to enhanced baseline inflammation associated with oxidative stress, related to various age-associated morbidities. A deficiency of Mg in rodents has been observed to impact the cell-mediated immunity and synthesis of IgG adversely. This deficiency can lead to various complications, such as lymphoma, histaminosis, hypereosinophilia, increased levels of IgE, and atrophy of the thymus. The immunological consequences of Mg deficiency in humans can be influenced by the genetic regulation of Mg levels in blood cells. Mg can also mediate cell cycle progression. There has been a renewed interest in the physiology and therapeutic efficacy of Mg. However, the in-depth mechanisms, their clinical significance, and their importance in malignancies and inflammatory disorders still need to be clarified. CONCLUSIONS: Mg is essential for optimal immune function and regulating inflammation. Deficiency in Mg can lead to temporary or long-term immune dysfunction. A balanced diet usually provides sufficient Mg, but supplementation may be necessary in some cases. Excessive supplementation can have negative impacts on immune function and should be avoided. This review provides an update on the importance of Mg in an immune response against cancer cells and infectious agents and how it regulates inflammation, oxidative stress, cell progression, differentiation, and apoptosis.

Recent advances in BCRP-induced breast cancer resistance treatment with marine-based natural products.

Breast cancer is the prominent cause of cancer-related death in women globally in terms of incidence and mortality. Despite, recent advances in the management of breast cancer, there are still a lot of cases of resistance to medicines, which is currently one of the biggest problems faced by researchers across the globe. Out of several mechanisms, breast cancer resistance protein (BCRP) arbitrated drug resistance is a major concern. Hormonal, cytotoxic and immunotherapeutic drugs are used in the systemic therapy of breast cancer. It is vital to choose drugs based on the clinical and molecular attributes of the tumor to provide better treatment with greater efficacy and minimal harm. Given the aforementioned necessity, the use of marine flora in treating breast cancer cannot be neglected. The scientists also stressed the value of marine-derived goods in avoiding breast cancer resistance. Future research into the identification of anticancer drugs will heavily draw upon the marine environment's ample supply of marine-derived natural products (MNPs), which have a wide range of biological functions. Cell cycle arrest, induction of apoptosis and anti-angiogenic, anti-proliferative and anti-metastasis actions are all part of their processes. The overview of breast cancer, the mechanisms underlying its resistance, recent clinical trials based on marine-derived products in breast cancer and the use of marine products in the treatment of breast cancer are highlighted in this paper. Moreover, the authors also emphasised the importance of marine-derived products in preventing breast cancer resistance.

Nano-mediated strategy for targeting and treatment of non-small cell lung cancer (NSCLC).

Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).

The Role of Natural Flavonoids as Telomerase Inhibitors in Suppressing Cancer Growth.

Cancer is a complex and multifaceted group of diseases characterized by the uncontrolled growth and spread of abnormal cells. While cancer can be challenging and life-altering, advances in research and development have led to the identification of new promising anti-cancer targets. Telomerase is one such target that is overexpressed in almost all cancer cells and plays a critical role in maintaining telomere length, which is essential for cell proliferation and survival. Inhibiting telomerase activity can lead to telomere shortening and eventual cell death, thus presenting itself as a potential target for cancer therapy. Naturally occurring flavonoids are a class of compounds that have already been shown to possess different biological properties, including the anti-cancer property. They are present in various everyday food sources and richly present in fruits, nuts, soybeans, vegetables, tea, wine, and berries, to name a few. Thus, these flavonoids could inhibit or deactivate telomerase expression in cancer cells by different mechanisms, which include inhibiting the expression of hTERT, mRNA, protein, and nuclear translocation, inhibiting the binding of transcription factors to hTERT promoters, and even telomere shortening. Numerous cell line studies and in vivo experiments have supported this hypothesis, and this development could serve as a vital and innovative therapeutic option for cancer. In this light, we aim to elucidate the role of telomerase as a potential anti-cancer target. Subsequently, we have illustrated that how commonly found natural flavonoids demonstrate their anti-cancer activity via telomerase inactivation in different cancer types, thus proving the potential of these naturally occurring flavonoids as useful therapeutic agents.

Synchronous multicentric giant cell tumour of immature skeleton with epiphysiometaphyseal origin.

Giant cell tumour of bone accounts for 5% of all primary bone tumours. Multicentric giant cell tumour is an infrequent variety be it either synchronous or metachronous accounting for less than 1% of all giant cell tumours. Synchronous multicentric giant cell tumour of foot and ankle with epiphysiometaphyseal origin is unheard of. We delineate a case of soap-bubble appearance lytic lesions at left distal tibia and talus in an early adolescent woman with biopsy proven giant cell tumour for its rarity and its successful management by extended curettage and allogenic impaction bone grafting.

Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases.

The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed suggest that the immunological state of the lung may be indirectly influenced by elements produced by the gut microbiota. SCFAs represent valuable potential therapeutic candidates in this context.

Impact of ecDNA: A mechanism that directs tumorigenesis in cancer drug Resistance-A review.

Extrachromosomal DNA (ecDNA) is often found in cancerous cells, and numerous scientific investigations have already shown that ecDNA-mediated oncogene amplification which contributes to cancer therapy resistance. This ecDNA is found to be essential for enhancing gene transcription and resistance to chemotherapeutic drugs, as well as promoting tumor heterogeneity and reversing tumor phenotypes, suggesting that it plays a key role in carcinogenesis. The ecDNA induces tumors to become hostile which results in a lower survival rate and chemotherapy tolerance. It also holds the potential as a target for treatment or diagnostic procedure of tumors. The review describes the properties and origins of ecDNA, as well as how it affects carcinogenesis, its function in cancer etiology and progression, and its therapeutic value. Propagation of oncogenes and resistance genes situated in extra-chromosomal DNA has been discovered to become one of the primary causes of intra-tumor genetic heterogeneity and may result in a threshold of probable evolutionary adaptation in many investigations.

A Shepherd's Crook Deformity of Proximal Femur Treated by Valgus Osteotomy and Bone Grafting.

The Shepherd's crook deformity of the proximal femur is a characteristic radiologic feature of fibrous dysplasia. It may be limited to a single bone, which is called monostotic, or may be polyostotic involving multiple bones as seen in McCune-Albright Syndrome. We report a case of a 19-year-old male patient who presented to us with pain in the right hip for one year. He had dysmorphic facies and multiple café-au-lait spots over the back, which were suggestive of McCune-Albright Syndrome. The radiographs of the hip showed varus deformity of the proximal femur. A lateral closing wedge osteotomy was done and the defect was filled with morselised femoral head allografts and fibular strut allografts. At the 14-month follow-up, the patient remained functionally active without any symptoms. The use of morselised femoral head allograft combined with strut fibular allograft ensures both stability and improved biology at the site of the lesion without any donor site morbidity.

Rapid Involution of Large Cardiac Rhabdomyomas With Everolimus Therapy.

Rhabdomyoma of the fetal heart is a rare disease accounting for about 1% of all fetal cardiac structural anomalies. They are often found in association with tuberous sclerosis complex. Large cardiac rhabdomyomas can compromise the cardiac function. We report a case of multiple large rhabdomyomas of the right and left ventricles, affecting the cardiac function, which was successfully treated with the chemotherapeutic and immunosuppressive medication everolimus, in a neonate with genetically confirmed tuberous sclerosis complex with multisystem manifestations. There was rapid involution of the tumors in response to everolimus therapy in this infant.

Ligand Decorated Primaquine Loaded Nanocarriers for Liver Targeting for Triggered Anti-Malarial Activity.

OBJECTIVE: The aim of the current research is to formulate a nano delivery system for effective delivery of primaquine for liver targeting to achieve the potential anti-malarial activity. Another objective of current development is to formulate a lactobionic acid conjugated polyphosphazene based nano delivery of primaquine for liver targeting to distinguish anti-malarial activity. METHOD: The particle size, entrapment efficiency, in-vitro drug release pattern, hepatotoxicity, MTT assay, erythrocyte toxicity assay, histopathology study, HepG2 cell uptake study, anti-- malarial study, and organ-distribution was also carried out to estimate the activity and potential features of a nanoparticle system. RESULTS: The results obtained from the above analysis justify the efficiency and effectiveness of the system. The NMR studies confirm the conjugation pattern and the TEM represents the spherical morphological features of nanoparticles. The controlled release pattern from the in-vitro release study was observed and found to be 73.25% of drug release in 20 hrs and in the nano-size range (61.6± 1.56 nm) by particle size analysis.SGOT level, SGPT, ALP, and Parasitemia level of optimized drug-loaded PEGylated lactobionic acid conjugated polyphosphazene derivatized nanoparticles (FF) was found to lie in the safe range, showing that the formulation is non-toxic to the liver. Primaquine drug-loaded PEGylated lactobionic acid conjugated polyphosphazene polymeric nanoparticles showed higher cell uptake on HepG2 cell lines as compared to the drug-loaded in PEGylated polyphosphazene polymeric nanoparticles and plain drug.Percentage cell viability of drugloaded PEGylated lactobionic acid conjugated polyphosphazene derivatized nanoparticles was decreased by enhancing the concentration of prepared nanoparticle system accessed by MTT assay. CONCLUSION: From the studies, it can be concluded that the optimized formulation of drug-loaded PEGylated lactobionic acid conjugated polyphosphazene derivatized nanoparticles showed high liver targeting, least toxicity to the liver, controlled release of the drug, higher anti-malarial activity against hepatocytes at a low dose, more effectiveness, and can be treated as a potential candidate for anti-malarial therapy.

Generation and validation of structurally defined antibody-siRNA conjugates.

Gene silencing by RNA interference (RNAi) has emerged as a powerful treatment strategy across a potentially broad range of diseases. Tailoring siRNAs to silence genes vital for cancer cell growth and function could be an effective treatment, but there are several challenges which must be overcome to enable their use as a therapeutic modality, among which efficient and selective delivery to cancer cells remains paramount. Attempts to use antibodies for siRNA delivery have been reported but these strategies use either nonspecific conjugation resulting in mixtures, or site-specific methods that require multiple steps, introduction of mutations, or use of enzymes. Here, we report a method to generate antibody-siRNA (1:2) conjugates (ARCs) that are structurally defined and easy to assemble. This ARC platform is based on engineered dual variable domain (DVD) antibodies containing a natural uniquely reactive lysine residue for site-specific conjugation to ß-lactam linker-functionalized siRNA. The conjugation is efficient, does not compromise the affinity of the parental antibody, and utilizes chemically stabilized siRNA. For proof-of-concept, we generated DVD-ARCs targeting various cell surface antigens on multiple myeloma cells for the selective delivery of siRNA targeting ß-catenin (CTNNB1). A set of BCMA-targeting DVD-ARCs at concentrations as low as 10 nM revealed significant CTNNB1 mRNA and protein knockdown.

Photobiomodulation Alleviates Postoperative Discomfort After Mandibular Third Molar Surgery.

PURPOSE: Surgical removal of mandibular third molars is associated with some degree of postoperative pain, trismus, and facial swelling. The purpose of the study was to evaluate the effect of photobiomodulation in reducing these postoperative side effects after surgical removal of mandibular third molars. MATERIALS AND METHODS: This randomized, double-blinded, split-mouth pilot study was carried out in the Department of Oral and Maxillofacial Surgery, Post Graduate Institute of Dental Sciences, Rohtak, India, among patients with impacted mandibular third molars. In each patient, 1 side was treated by photobiomodulation and the other side received placebo. Photobiomodulation was performed by intraoral and extraoral application of an 830-nm and 30-mW laser at different time points. Pain, trismus, and facial swelling were evaluated at all time points. The number of analgesics taken also was recorded. The data were analyzed using descriptive, bivariate and multivariate statistics. RESULTS: The study was conducted in 25 patients (56% male patients) with a mean age of 22.16 ± 4.60 years. There were 50 sites divided equally into both groups. The sites treated with photobiomodulation showed a significant reduction in pain and swelling (P < .05) compared with the sites in the placebo group. Moreover, an increase in mouth opening was noted after photobiomodulation compared with that in the placebo group, but this was not statistically significant (P > .05). CONCLUSIONS: The results of this study suggest that photobiomodulation is effective in reducing pain and swelling after mandibular third molar surgery. Hence, it can be used as an alternative and effective modality after surgical removal of mandibular third molars, thereby improving the quality of life of the patients.

Purse String Suture Closure: A Useful Double-Layer Technique for Closure of an Oronasal Communication.

INTRODUCTION: Various treatment modalities are reported in the literature for the management of oronasal communication. Single-layer closure often leads to failure and persists a major concern to an operative surgeon. Therefore, double-layer closure is one of the keys to successful management of oronasal communication. METERIAL AND METHOD: A continuous intramucosal running purse string suture at submucosal depth was placed circumferentially around the defect margin with 3-0 round body polyglactin suture as a first layer. Pedicled palatal rotation axial flap based on greater palatine artery was used as the second layer of closure, above the first palatal submucosal layer. CONCLUSION: Intramucosal purse string suture technique provides adjacent local tissue for closure of oronasal communication. This technique is easy and can be used as an alternative option for double-layered closure of an oronasal communication, without donor site morbidity and minimal patient discomfort.

Significantly Enhanced Energy Density by Tailoring the Interface in Hierarchically Structured TiO2-BaTiO3-TiO2 Nanofillers in PVDF-Based Thin-Film Polymer Nanocomposites.

Dielectric polymer nanocomposites with a high breakdown field and high dielectric constant have drawn significant attention in modern electrical and electronic industries due to their potential applications in dielectric and energy storage systems. The interfaces of the nanomaterials play a significant role in improving the dielectric performance of polymer nanocomposites. In this work, polydopamine (dopa)-functionalized TiO2-BaTiO3-TiO2 (TiO2-BT-TiO2@dopa) core@double-shell nanoparticles have been developed as novel nanofillers for high-energy-density capacitor applications. The hierarchically designed nanofillers help in tailoring the interfaces surrounding the polymer matrix as well as act as individual capacitors in which the core and outer TiO2 shell function as a capacitor plate because of their high electrical conductivity while the middle BT layer functions as a dielectric medium due to high dielectric constant. Detailed electrical characterizations have revealed that TiO2-BT-TiO2@dopa/poly(vinylidene fluoride) (PVDF) possesses a higher relative dielectric permittivity (εr), breakdown strength ( Eb), and energy density as compared to those of PVDF, TiO2/PVDF, TiO2@dopa/PVDF, and TiO2-BT@dopa/PVDF polymer nanocomposites. The εr and energy density of TiO2-BT-TiO2@dopa/PVDF were 12.6 at 1 kHz and 4.4 J cm-3 at 3128 kV cm-1, respectively, which were comparatively much higher than those of commercially available biaxially oriented polypropylene having εr of 2.2 and the energy density of 1.2 J cm-3 at a much higher electric field of 6400 kV cm-1. It is expected that these results will further open new avenues for the design of novel architecture for high-performance polymer nanocomposite-based capacitors having core@multishell nanofillers with tailored interfaces.

Heparin appended ADH-anionic polysaccharide nanoparticles for site-specific delivery of usnic acid.

The intention of present research work is to formulate usnic acid (UA) loaded heparin modified gellan gum (HAG) nanoparticles (NPs). HAG copolymer based conjugation was synthesized and characterized by 1H NMR and FT-IR spectroscopy. Plain and UA loaded HAG NPs were prepared via nanoprecipitation technique. NPs were typified and further characterized for particle size, polydispersity index, entrapment efficiency, zeta potential, atomic force microscopy, differential scanning calorimetry, X-ray diffraction analysis, and in-vitro release. In-vitro tube formation assay, tumorsphere assay, autophagy assay, DNA cleavage assay, internalization by confocal and FACS based internalization analysis, caspase assay and cell cycle assay were performed for biological activity. Obtained experimental results explored that HAG NPs displayed a sustained release of UA (95.67% in 48 h) compared to gellan gum NPs (96.12% in 8 h). In cytotoxicity studies, UA loaded HAG NPs exhibited an enormous cytotoxic potential against A549 cancer cells. In the in vivo bio-distribution study, using albino rat model the free UA concentration was found 7.09 ±â€¯0.9%, 2.7 ±â€¯1.5%, 7.5 ±â€¯2.1, 9.2 ±â€¯2%, and 6.25 ±â€¯1.3% post two hours of intravenous administration, however, in the case of UA loaded HAG NPs the obtained level was 4.1 ±â€¯1.10, 7.7 ±â€¯1.30%, 2.21 ±â€¯0.29%, 1.85 ±â€¯0.25%, 2.2 ±â€¯0.78%, 2.9 ±â€¯1.21% respectively, in heart, lung, liver, spleen, intestine and kidney. The overall anticancer study and result of internalization deciphered the higher anticancer potential of UA loaded HAG NPs.

Incidence and factors influencing the spontaneous closure of Fontan fenestration.

INTRODUCTION: The Fontan operation is the final stage of single ventricle palliation in patients with complex congenital heart disease. Fenestration in the Fontan conduit, providing an atrial level right to left shunt, has been shown to reduce early postoperative morbidity. However, there is limited data on the long-term fate of this fenestration. The aim of this study is to define the rate of spontaneous closure of the fenestration in the Fontan conduit and factors predictive of the fate of the fenestration. METHODS: This was a retrospective study reviewing the medical records of the patients who underwent fenestrated Fontan operation at our center. Preoperative, intraoperative and postoperative variables including the status of the Fontan fenestration were extracted and analyzed. RESULTS: Of 67 patients included in the study, 15 (22%) had spontaneous closure of the fenestration. Of the remaining 52 patients, 11 (20%) had procedural closure of this fenestration (10 via cardiac catheterization and 1 via surgery) at a median duration of 3 months after the Fontan operation. Patients with higher preoperative pulmonary vascular resistance and a history of postoperative systemic venous thromboembolism had higher likelihood of having persistence of the fenestration with P value of .045 and .037, respectively. CONCLUSIONS: The rate of spontaneous closure of the Fontan fenestration was 22% in our study. Elevated preoperative pulmonary vascular resistance and history of systemic venous thromboembolism are predictive of persistent Fontan fenestration.