An insight for the inhibition of anxiolytic and anti-convulsant effects in zebrafish using the curcumins via exploring molecular docking and molecular dynamics simulations.

In the contemporary landscape, anxiety and seizures stand as major areas of concern, prompting researchers to explore potential drugs against them. While numerous drugs have shown the potential to treat these two neurological conditions, certain adverse effects emphasize the need for development of safer alternatives. This study seeks to employ an in silico approach to evaluate natural compounds, particularly curcumins, as potential inhibitors of GABA-AT to mitigate anxiety and seizures. The proposed methodology includes generating a compound library, minimizing energy, conducting molecular docking using AutoDock, molecular dynamics simulations using Amber, and MM-GBSA calculations. Remarkably, CMPD50 and CMPD88 exhibited promising binding affinities of - 9.0 kcal/mol and - 9.1 kcal/mol with chains A and C of GABA-AT, respectively. Further, MM-GBSA calculations revealed binding free energies of - 10.88 kcal/mol and - 10.72 kcal/mol in CMPD50 and CMPD88, respectively. ADME analysis showed that these compounds contain drug-likeness properties and might be considered as potential drug candidates. The findings from this study will have practical applications in the field of drug discovery for the development of safer and effective drugs for treatment of anxiety and seizures. Overall, this study will lay the groundwork for providing valuable insights into the potential therapeutic effects of curcumins in alleviating anxiety and seizures, establishing a computational framework for future experimental validation.

Short segment posterior fixation of unstable thoracolumbar vertebral fractures with fractured vertebra augmentation with intermediate pedicle screw - a clinicoradiological analysis.

INTRODUCTION: Unstable thoracolumbar burst fractures are routinely encountered in orthopedic practice. Recently, short-segment fixation with pedicle screw augmentation of the fractured vertebra for unstable thoracolumbar burst fractures has gained popularity. Nonetheless, the maintenance of the kyphotic correction during the follow-up period remains controversial. This study aimed to examine the clinical-radiological outcomes, complications, and functional outcomes of fractured vertebrae augmentation with intermediate pedicle screws in short-segment instrumentation in acute thoracolumbar spine fractures. METHODS: This retrospective study was conducted in the Department of Orthopedics, All India Institute of Medical Sciences, Jodhpur, using medical records from January 2021 to October 2022. Parameters such as local kyphosis correction, loss of kyphotic correction at final follow-up, anterior body height correction (%), and loss of correction (%) at final follow-up were measured as primary outcomes. Various other parameters such as operative time, blood loss, length of hospital stay, and visual analog scale were measured as secondary outcomes. RESULTS: The mean correction obtained via surgery in the immediate postoperative period was 13.7±2.3 degrees. The mean loss of correction at the final follow-up was 4.1±2.0 degrees, and the mean final local kyphotic angle was 7.2±2.4 degrees (P<0.05). The mean correction obtained via surgery in the immediate postoperative period was 37.2%±9.0%. The mean loss of correction at the final follow-up was 10.5%±5.3%, and the mean final anterior vertebral body height maintained was 72%±11.0% (P<0.05). CONCLUSION: Short-segment posterior fixation with pedicle screw augmentation achieves good correction of local kyphotic angle and anterior vertebral height in the immediate postoperative period, but some loss of correction at final follow-up is common. In our study, the loss of correction corresponded directly to the load-sharing score.

Discovery of a Novel Yadav-Kunal Reflex in Context of Upper Motor Neuron Lesions: A Report of Three Cases.

Introduction: Numerous reflexive responses have been documented as alterations to the Babinski sign within upper motor neuron lesions. However, scant attention has been given to reflexes beyond these, which exhibit independence from the extensor plantar response. These reflexes predominantly form polysynaptic arcs, with nociceptive stimuli acting as afferents. Case Report: The reflex was serendipitously discovered in an 18-year-old female patient who presented with spastic paraplegia with bowel and bladder involvement, as a consequence of an aneurysmal bone cyst of the D3 (dorsal) vertebrae, and the same was named after the authors as "Yadav-Kunal reflex" which can be defined as: "In individuals with spastic paraparesis, forcibly plantarflexing the toes will result in sudden jerky flexion of the knee and hip on the same side." This novel reflex was further investigated and validated in two additional patients with spastic paraplegia: one, a 45-year-old female with D9-D10 Pott's spine and bowel and bladder involvement, and the other, a 65-year-old male with D10-D11 compressive myelopathy and bowel and bladder involvement. This reflex was meticulously tracked until the abatement of spasticity following surgical intervention. Notably, its manifestation was evident in individuals experiencing spastic paraparesis, dissipating concomitantly with the resolution of spasticity - a direct clinical correlation. Conversely, the reflex was conspicuously absent in cases of flaccid paraplegia. Conclusion: Spasticity, characterized by an increase in muscle tone on swift stretching movements, is a manifestation of a stretch reflex disorder. This condition is primarily induced by lesions affecting upper motor neurons. The activation of muscle spindles in toe dorsiflexors (primarily governed by the L5 nerve) occurs during forceful elongation caused by plantarflexion.

Multifocal lower limb hemangioendothelioma in a young female: a case report and review of the literature.

A 26-year-old female presented with pain and swelling of distal thigh and distal leg. She was diagnosed with multifocal epitheloid hemangioendothelioma (EHE) and was successfully treated with wide resection of femoral and tibial lesions followed by their reconstruction using vascularised fibular graft and local bone grafting. One year into follow-up, the patient remained asymptomatic with full Range Of Motion (ROM) and full weight bearing walking. This case illustrates a unique multifocal presentation of hemangioendothelioma and early surgical intervention leading to complete recovery, highlighting the importance of early diagnosis and intervention to help improve prognosis and quality of life of the patient.

Drug Product Formulation and Fill/Finish Manufacturing Process Considerations for AAV-based Genomic Medicines.

Adeno-associated viruses (AAVs) have become the delivery medium of choice for a variety of genomic medicine applications i.e., gene therapy, gene editing/regulation, and ex-vivo cell therapy. AAVs are protein-DNA complexes which have unique stability characteristics that are susceptible to various stress exposure conditions commonly seen in the drug product (DP) life cycle. This review takes a comprehensive look at AAV DP formulation and process development considerations that could impact critical quality attributes (CQAs) during manufacturing, packaging, shipping, and clinical use. Additional aspects related to AAV development reviewed herein are: (1) Different AAV serotypes with unique protein sequences and charge characteristics potentially leading to discrete stability profiles; (2) Manufacturing process challenges and optimization efforts to improve yield, recovery and purity especially during early development activities; and (3) Defining and identifying CQAs with analytical methods which are constantly evolving and present unique characterization challenges for AAV-based products.

Functional outcome and analysis of factors affecting health-related quality of life of surgically managed pelvic ring fractures: a cross-sectional study.

INTRODUCTION: Pelvic ring fractures, particularly those involving the posterior pelvis, pose significant challenges due to their inherent instability. The posterior pelvic ring is critical in providing structural support and stability to the pelvis. This study evaluates the functional outcomes and health-related Quality of life (HRQOL) of patients who underwent internal fixation for unstable pelvic fractures. Various factors influencing the outcomes are also investigated. MATERIAL AND METHODS: A single-center cross-sectional study was conducted on patients with unstable sacral fractures treated with posterior tension band plate or sacroiliac plating with or without symphyseal plating between 2016 and 2020. Patient demographics, injury mechanisms, associated injuries, surgical details, complications, and return-to-work data were collected. HRQOL was assessed using specific pelvic fracture instruments and general HRQOL questionnaires. Logistic regression analysis was performed to identify factors associated with lower SF-12 and SF-36 scores RESULTS: The study included 54 patients, predominantly males (55.6%), aged 18-70 years, with high-energy trauma mechanisms, such as road traffic accidents and occupational injuries. The majority of patients had lateral compression pelvic fractures. Overall, the functional outcomes were favorable, with excellent or good outcomes observed in 86.1% of cases. Patients with associated injuries, such as abdominal, chest, or head injuries, were likelier to have lower SF-12 physical component scores. Sexual satisfaction scores remained stable for most patients post-surgery. DISCUSSION: This study highlights the favorable functional outcomes and HRQOL for patients undergoing fixation for unstable pelvic ring fractures. Younger, working-age males were the most commonly affected demographic. Associated injuries significantly affected physical HRQOL scores. Despite high-energy trauma, patients generally reported satisfactory sexual function post-surgery.

Antibacterial activity of hydrophobicity modulated cationic polymers with enzyme and pH-responsiveness.

The membrane lipid compositions of prokaryotic and eukaryotic cells are inherently different in many aspects, although some similarities exist in their structure and composition. Therefore, selective targeting of membrane lipids with a compound of therapeutic value, such as an antibacterial copolymer, is often challenging. Hence, developing an ideal copolymer with antibacterial properties demands hydrophobicity/hydrophilicity balance with a high biosafety profile. To integrate hydrophobic/hydrophilic balance and cationic charge in an alternating antibacterial copolymer with enzyme and pH-responsiveness, a lysine appended styrenic monomer was copolymerized with a fatty acid (octanoic acid (OA) or myristic acid (MA)) tethered maleimide monomer via reversible addition-fragmentation chain transfer (RAFT) polymerization. A range of microscopic analyses, including dynamic light scattering (DLS), confirmed the formation of nanoaggregates (size ∼30-40 nm) by these polymers in aqueous solution with positive zeta potential (cationic surface charge). Hydrophobic Nile red (NR) dye was successfully encapsulated in the nanoaggregates, and the in vitro release kinetics of the NR dye were monitored at different pHs and in the presence or absence of esterase/lipase. The in vitro release kinetics of NR revealed ∼85% dye release in the presence of pH 5.5 and lipase, suggesting their suitability for pH/enzyme-triggered therapeutic payload delivery. The standard broth microdilution assay showed significant bactericidal activity against both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria with an MIC50 value <30 µg mL-1. The effect of polymeric nanoaggregates on bacterial morphology and in vitro survival was further confirmed by field emission scanning electron microscopy (FESEM), agar gel disk diffusion assay, and bacterial live/dead cell count. The significantly low hemolytic activity against red blood cells (RBCs) (HC50 >103 µg mL-1) and nontoxic effect on human intestinal epithelial cells (INT 407) (EC50 >500 µg mL-1) ensure that the polymer nanoaggregates are safe for in vivo use and can serve as a potent antibacterial polymer.

Does the pararectus approach have better outcomes and fewer complications than the modified Stoppa approach for the fixation of acetabular fractures in adults: A systematic review and meta-analysis?

BACKGROUND: The pararectus approach is a minimally invasive surgical approach for anterior acetabulum fracture, with an advantage of the medial window of the modified Stoppa approach (MSA). However, it is unclear whether the pararectus approach is superior to MSA. We aimed this systematic review and meta-analysis to compare the outcomes and complications of pararectus and MSA. METHODS: We performed a data search by conducting an electronic search across databases of PubMed, Embase, Scopus, Cinahl, CNKI, and Cochrane Library and included seven comparative studies for analysis. Statistical analysis was performed using the RevMan software 5.4.1. The risk of bias was evaluated using the Cochrane Collaboration's risk of bias tool for RCTs and the MINORS tool for non-RCTs. RESULTS: Two randomized control trials (RCTs), one prospective study, and four retrospective studies were included. Meta-analysis revealed a better Matta's reduction quality [OR 1.58, 95% CI 1.06, 2.37; p = 0.03] and radiological outcome [OR 2.18, 95% CI 1.03, 4.60; p = 0.04] in MSA than in pararectus approach. However, the pararectus approach has less intraoperative blood loss [MD - 9.79 (95% CI - 176.75, - 6.83; p = 0.03)] and a shorter hospital stay [MD - 2.61 (95% CI - 5.03, - .18; p = 0.04)] than MSA. Both approaches have failed to show a difference concerning overall complication rates [OR 0.66 (95% CI 0.28, 1.55; p = 0.34)], postoperative infection, DVT, duration of surgery [MD - 15.09 (95% CI - 35.38, 5.20; p = 0.15)], functional outcome, and incision length. CONCLUSION: The pararectus approach offers an advantage with lesser operative blood loss and shorter hospital stay, whilst MSA stands out with better reduction quality and radiological outcomes. Nevertheless, both approaches exhibit no difference in complication rates, duration of surgery, incision length, and functional outcome. Hence, the pararectus approach can be considered an alternative to MSA; however, the existing literature fails to demonstrate a distinct advantage over MSA.

Malignant giant cell tumour of distal ulna.

Giant cell tumour (GCT) accounts for 5% of all primary bone tumours. GCT in the distal third of ulna is quite rare. We present a case of recurrent GCT in distal third of ulna with malignant features involving tenosynovium. The case was treated by wide resection of tumour and on follow up, patient recovered well with no evidence of further recurrence. Considering the features, according to the literature reviewed, is the first case of its type.

Pathological fracture treated with total femoral replacement in a case of chondrosarcoma involving the entire-length femoral shaft.

INTRODUCTION AND IMPORTANCE: We here present a case of chondrosarcoma of the diaphysis of the femur with extensive involvement of the length of the bone and with the pathological fracture at the mid-shaft level. Total femur replacement was done in this case with a bipolar head and repair of abductors and hip flexors to the implanted prosthesis. CASE PRESENTATION: An elderly female in her late 60s presented to the trauma department with sudden onset pain and inability to bear weight on her left lower limb following a trivial slip and fall. The Radiographs revealed a pathological spiral mid-shaft displaced fracture of the femur with an extensive mixed lesion throughout the femur. Magnetic Resonance imaging revealed involvement of more than 90% of the femur with lesion extension into the quadriceps and hamstrings. Histopathology confirmed grade-II conventional chondrosarcoma. Metastatic work-up showed no distant spread. Wide-local resection and total femur endo-prosthetic reconstruction were done. No recurrence or infection was evident at the 18-month follow-up. In elderly non-metastatic pathological fractures, limb salvage with endo-prosthetic reconstruction can be a preferred treatment. CLINICAL DISCUSSION: This case is unique in describing a rare presentation of chondrosarcoma of the diaphysis of the femur, which eventually landed in a pathological fracture. The fracture may increase the tumour's aggressiveness, but wide-margin resection should be the mainstay treatment for primary or recurrent chondrosarcoma, irrespective of pathological fracture. CONCLUSION: In well-indicated cases (no distant spread - N0M0 disease), Total Femur Replacement (TFR) is an excellent option for limb salvage in tumours with extensive involvement of the femur.

Chronic neck pain in a child: a case of osteoblastoma of the C5 cervical vertebra.

Osteoblastoma is a primary bone-forming tumour that usually occurs in the second decade with an affinity to the posterior elements when found in the spine. Its occurrence in the early first decade is uncommon and often causes a diagnostic dilemma. It usually has a late presentation and the symptoms may be non-specific which may lead the clinician to overlook this particular entity. We present a case of osteoblastoma of the posterior elements of the C5 vertebra in a pre-adolescent child who was diagnosed and successfully managed with surgical resection in a timely fashion that led to favourable recovery postoperatively.

Gelatin-decorated Graphene oxide: A nanocarrier for delivering pH-responsive drug for improving therapeutic efficacy against atherosclerotic plaque.

The progressive inflammatory disease atherosclerosis promotes myocardial infarction, stroke, and heart attack. Anti-inflammatory drugs treat severe atherosclerosis. They are inadequate bioavailability and cause adverse effects at higher doses. A new nanomaterial coupled pH-apperceptive drug delivery system for atherosclerotic plaque is outlined here. We have synthesized a Graphene Oxide-Gelatin-Atorvastatin (GO-Gel-ATR) nanodrug characterized by spectroscopic and imaging techniques. The encapsulation efficiency of GO-Gel-ATR (79.2%) in the loading process is observed to be better than GO-ATR (66.8%). The internal milieu of the plaque cells has a pH of 6.8. The GO-Gel-ATR displays sustained and cumulative release profile at pH 6.8 compared to ATR and GO-ATR. Our proposed nanocomposite demonstrated high cytocompatibility up to 100µg/mL in foam cells induced by Oxidized-Low Density Lipoprotein (Ox-LDL) and Lipopolysaccharides (LPS) compared to normal macrophages for 24 and 48 h. The uptake efficacy of the nanodrugs is shown to be enhanced in foam cells compared to normal macrophage. Oil red O staining of foam cells with and without drugs confirmed therapeutic efficacy. Foam cells treated with nanocomposite had more lipids efflux than ATR. The finding of the in-vitro study reveals that the GO-Gel-ATR nanocomposite carriers have the potential to deliver anti-atherosclerotic drugs effectively and inhibit atherosclerotic plaque progression.

A systemic review and meta-analysis of pararectus versus ilioinguinal approach for the management of acetabular fractures.

PURPOSE: The complex anatomy of acetabular fracture needs a surgical approach that can achieve anatomical reduction with fewer complications for the fixation of these fractures. Current literature suggests that both Pararectus (PR) approach and Ilioinguinal (IL) approach can be used for the fixation of these fractures safely. However, superiority of the PR approach over the IL approach is not established. Hence, this meta-analysis aimed to compare the PR versus IL approach. METHODOLOGY: A literature search was performed on five databases Medline/PubMed, Scopus Embase, Cinhal, and Cochrane Library, from the inception to January 14, 2023. A qualitative and quantitative analysis was done for the five eligible studies from the literature search. Individual study characteristics data and outcomes were extracted, and Software version 5.4.1 of Review Manager was used for statistical analysis. RESULTS: Five articles, one Randomized trial (RCT), and four retrospective articles were included and analyzed in this meta-analysis. PR approach has a shorter surgical time [mean difference (MD) -48.4 with 95% CI -74.49, -22.30; p = 0.0003], less intraoperative blood loss (MD -123.22 with 95% CI -212.28, -34.15; p = 0.007), and smaller surgical incision (MD -9.87 with 95% CI -15.21, -4.52; p = 0.0003) than the IL approach. However, the meta-analysis failed to show a difference between the two surgical approaches concerning the quality of reduction, overall complications, nerve injury, vascular injury, heterotopic ossification, deep vein thrombosis, and pulmonary embolism. CONCLUSION: The PR approach has a shorter surgical duration, less blood loss, and a smaller surgical incision than the IL approach. However, both surgical approaches have equivocal results regarding fracture reduction quality, complication rates, and functional outcomes for acetabular fracture fixation. Hence, for acetabular fractures fixation, PR approach can be considered a safe and feasible alternative to the IL approach.

Rituximab as add-on therapy in patients with resistant lupus nephritis who have failed induction or maintenance therapy with other agents: A real-world experience from a single center in Mumbai.

BACKGROUND: Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies. OBJECTIVE: The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN. METHODS: Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections. RESULTS: The median age was 28 years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075 mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6 months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12 months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6 months, Regimen-1 (500 mg every 6 months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1 g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6 months.At a median follow-up of 29 months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data. CONCLUSION: Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1 year, underscoring the need for optimized maintenance therapy.

Invasive fungal infection in ANCA-associated vasculitis: Between the Devil and Deep blue sea. Case series and review of the literature.

INTRODUCTION: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are susceptible to opportunistic infections, including invasive fungal infections (IFI). This is due to many factors, including prolonged immunosuppressive therapy. The treatment of AAV with such IFIs is challenging. METHODS: A descriptive analysis of 5 patients with AAV complicated by concomitant invasive fungal infections was performed. We also have done a comprehensive literature review of IFIs in AAV using PubMed and Google Scholar databases. RESULTS: All 5 patients initially received immunosuppressive medication but subsequently acquired IFI. One patient had sphenoid sinus involvement, and four had lung parenchymal involvement. Aspergillus infection was diagnosed in three patients, Cryptococcus infection in one patient and mixed infection with Aspergillus and Mucor infection in one patient. All our patients were on low doses of corticosteroids for several months to years or had received high-dose pulse steroids with cyclophosphamide in the last few weeks before being diagnosed with IFI. It was difficult to distinguish disease activity from IFI in all the cases. Two of the five patients died despite antifungal therapy. The literature review revealed a prevalence of IFIs ranging from 1 to 9.6% (excluding pneumocystis pneumonia). Aspergillosis was the predominant type of IFI, affecting 46 of 86 patients. Most of these patients (40/46) had pulmonary involvement. The prognosis for patients with IFI was consistently poor, as evidenced by 19 deaths out of 29 reported outcomes. CONCLUSION: Overall, IFIs have a poor prognosis in patients with AAV. Differentiating disease activity from IFI is difficult because of similar organ distribution, imaging lesions, and histopathological characteristics. A high suspicion index and good-quality microbiology are needed for early treatment and prevention of mortality.

Primary Ewing's sarcoma of the talus.

Ewing's sarcoma is a malignant round cell tumour of bones and soft tissues that usually arises from the diaphyseal or meta-diaphyseal parts of long bones and less commonly from flat bones. It occurs rarely in the foot and if occurs, the calcaneus and the metatarsals are commonly involved. We present a case of a young woman diagnosed with primary Ewing's sarcoma of the talus with local spread to adjacent tarsals and the ankle joint. Ewing's sarcoma of feet, if present with even a trivial suspicion of spread either locally or distant, makes limb salvage surgery difficult. So, the treatment with radical surgery or by combined chemotherapy and radiotherapy should be considered-keeping in mind the complex anatomy of the foot and the difficulty in achieving tumour-free margins. Based on this experience, she underwent below-knee amputation. The patient received adjuvant chemotherapy and survived with a disease-free survival at the latest follow-up of 1 year.

A rare presentation of recurrent chondroblastoma of scapula, acromion and lateral end of clavicle.

About 1% of primary bone tumours are chondroblastoma, which develop from secondary ossification centers of long bones, preferably. The scapula, clavicle, and acromion are the rarest sites for this tumour. The recurrence rate is 14-18%, depending on the site of origin. There are various treatment options, but extended curettage and bone grafting are the main treatment modalities for chondroblastoma. In cases of recurrence, marginal excision and wide local excision are the treatments used. Here we report a recurrent tumour in that location that was removed by wide local excision. After 2 years of follow-up, there were no signs or symptoms of recurrence noted. This case is notable for its rare site of occurrence and successful surgical management without any episodes of re-occurrence after a 2-year follow-up period.

The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection.

BACKGROUND: The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to drive immune activation of multiple antiviral host factors has been progressively recognized. Among them, Type III Interferons (IFNs) exhibit a pivotal role in inducing potent antiviral host responses by upregulating the expression of several antiviral genes, including the Interferon-Stimulated Genes (ISGs) that specifically target the virus replication machinery. To harness the immuno-adjunctive potential, we examined whether pre-treatment of IFNλ3, a Type III IFN, can activate antiviral host responses against IAV infections. METHODS: In the present study, we bioengineered a food-grade lactic acid-producing bacteria (LAB), Lactococcus lactis (L. lactis), to express and secrete functional murine IFNλ3 (MuIFNλ3) protein in the extracellular milieu. To test the immune-protective potential of MuIFNλ3 secreted by recombinant L. lactis (rL. lactis), we used murine B16F10 cells as an in vitro model while mice (BALB/c) were used for in vivo studies. RESULTS: Our study demonstrated that priming with MuIFNλ3 secreted by rL. lactis could upregulate the expression of several antiviral genes, including Interferon Regulatory Factors (IRFs) and ISGs, without exacerbated pulmonary or intestinal inflammatory responses. Moreover, we also showed that pre-treatment of B16F10 cells with MuIFNλ3 can confer marked immune protection against mice-adapted influenza virus, A/PR/8/1934 (H1N1) infection. CONCLUSION: Since the primary target for IAV infections is the upper respiratory and gastrointestinal tract, immune activation without affecting the tissue homeostasis suggests the immune-adjunctive potential of IFNλ3 against IAV infections.