Increased Cellular Dosage of Bone Marrow Aspiration Concentrate Does Not Translate to Increased Clinical Effectiveness in Knee Osteoarthritis: A Phase I Dose Escalation Study.

Introduction: Knee osteoarthritis (KOA), a chronic degenerative disease, significantly impairs quality of life due to pain and mobility limitations. Traditional treatments focus on symptom management without addressing the underlying disease progression, leading to a growing interest in regenerative medicine approaches. Bone marrow aspirate concentrate (BMAC), rich in mesenchymal stem cells and growth factors, has shown potential for cartilage repair and symptom relief in KOA. Despite promising outcomes, the optimal BMAC dosage for knee OA treatment remains undetermined. This study aims to evaluate the clinical efficacy and safety of varying BMAC dosages in knee OA treatment. Methods: This prospective controlled dose-escalation study involved 75 patients with early-stage knee OA, categorized into three groups based on BMAC dosage administered 10 × 106 cells (low-dose group), 50 × 106 cells (medium-dose group), or 100 × 106 cells (high-dose group). All the patients underwent a single intra-articular injection of BMAC and were monitored over a year. The primary outcomes include Visual Analog Scale (VAS) for pain and the Knee Injury and Osteoarthritis Outcome Score (KOOS) for joint function recorded at baseline, 1, 3, 6, and 12 months post-intervention. Adverse events were also documented. Results: Significant clinical improvements in VAS and KOOS scores were noted across all groups at all time points compared to the baseline. However, these improvements did not significantly differ between dosage groups throughout the follow-up period. Adverse effects were minimal and primarily consisted of transient post-injection pain and effusion, with no dose-dependent increase in complications. Conclusion: BMAC treatment for knee OA is safe and demonstrates potential for significant pain relief and functional improvement, irrespective of the dosage administered within the tested range. The lack of significant differences among varying dosages suggests a plateau in therapeutic efficacy beyond a certain threshold. Further research is necessary on the long-term outcomes to optimize the dosing strategy.

Effect of Cellular Dosage of Bone Marrow Aspiration Concentrate on the Radiological Outcomes in Knee Osteoarthritis: A Phase I Dose-Escalation Study.

Introduction: Knee osteoarthritis(KOA), a chronic degenerative disease, significantly impairs quality of life due to pain and mobility limitations. Traditional treatments focus on symptom management without addressing the underlying disease progression, leading to a growing interest in regenerative medicine approaches. Bone marrow aspirate concentrate (BMAC), rich in mesenchymal stem cells and growth factors, has shown potential for cartilage repair and symptom relief in KOA. Despite promising outcomes, the optimal BMAC dosage for knee OA treatment remains undetermined. This study aims to evaluate the radiological outcomes of varying BMAC dosages in knee OA treatment. Methods: This prospective controlled dose-escalation study involved 75 patients with early-stage knee OA, categorized into three groups based on BMAC dosage administered 10x106 cells (low-dose group), 50 × 106 cells (medium-dose group), or 100x106 cells (high-dose group). All the patients underwent a single intra-articular injection of BMAC and were monitored over a year. The primary outcomes include magnetic resonance observation of cartilage repair tissue (MOCART 2.0) score to assess the cartilage. Results: We noted significant improvement in the overall MOCART score (p = 0.027) and subchondral change sub-score (p = 0.048) and defect filling sub-score (p = 0.025) in the medium- and high-dose cohorts compared to the low-dose cohort at 1 year follow-up. Although we noted positive correlation between the clinical and radiological outcome (r = 0.43), we did not find any significant different in the clinical outcome between the treatment groups. Conclusion: BMAC for OA knee resulted in significant improvement in the radiological scores compared to the baseline. Medium and high doses of BMAC result in significantly higher radiological scores compared to low-dose BMAC at 1 year. However, the radiological improvement did not translate into functional improvement, irrespective of the dosage administered at 1 year. Further research is necessary on the long-term outcomes to understand and optimize the dosing strategy based on clinico-radiological results.

Tubulin Vibration Modes Are in the Subterahertz Range, and Their Electromagnetic Absorption Is Affected by Water.

Many proteins are thought to coordinate distant sites in their structures through a concerted action of global structural vibrations. However, the direct experimental spectroscopic detection of these vibration modes is rather elusive. We used normal-mode analysis to explore the dominant vibration modes of an all-atom model of the tubulin protein and described their characteristics using a large ensemble of tubulin structures. We quantified the frequency range of the normal vibrational modes to be in the subterahertz band, specifically between ∼40 and ∼160 GHz. Adding water layers to the model increases the frequencies of the low-frequency modes and narrows the frequency variations of the modes among the protein ensemble. We also showed how the electromagnetic absorption of tubulin vibration modes is affected by vibrational damping. These results contribute to our understanding of tubulin's vibrational and electromagnetic properties and provide a foundation for future attempts to control protein behavior via external electromagnetic fields.

Exploring a facile preparation method for Co-Ni/MoS2-derived nanohybrid from wheat straw extract and its physicochemical properties.

This study presents a novel approach for the fabrication of a Co,Ni/MoS2-derived nanohybrid material using wheat straw extract. The facile synthesis method involves a sol-gel process, followed by calcination, showcasing the potential of agricultural waste as a sustainable reducing and chelating reagent. The as-prepared nanohybrid has been characterized using different techniques to analyse its physicochemical properties. X-ray diffraction analysis confirmed the successful synthesis of the nanohybrid material, identifying the presence of NiMoO4, CoSO4 and Mo17O47 as its components. Fourier-transform infrared spectroscopy differentiated the functional groups present in the wheat straw biomass and those in the nanohybrid material, highlighting the formation of metal-oxide and sulphide bonds. Scanning electron microscopy revealed a heterogeneous morphology with agglomerated structures and a grain size of around 70 nm in the nanohybrid. Energy-dispersive X-ray spectroscopy analysis shows the composition of elements with weight percentages of (Mo) 9.17%, (S) 6.21%, (Co) 12.48%, (Ni) 12.18% and (O) 50.46% contributing to its composition. Electrochemical analysis performed through cyclic voltammetry showcased the exceptional performance of the nanohybrid material as compared with MoS2, suggesting its possible applications for designing biosensors and related technologies. Thus, the research study presented herein underscores the efficient utilization of natural resources for the development of functional nanomaterials with promising applications in various fields. This study paves a way for manufacturing innovation along with advancement of novel synthesis method for sustainable nanomaterial for future technological developments.

Combinatorial Delivery of Docetaxel- and Erlotinib-Loaded Functionalized Nanostructured Lipid Carriers for the Treatment of Triple-Negative Breast Cancer Using Quality-by-Design Approach.

This study explored the combined administration of docetaxel (DOC) and erlotinib (ERL) using nanostructured lipid carriers (NLCs), with folic acid (FA) conjugation to enhance their synergistic anticancer efficacy against triple-negative breast cancer. NLCs were developed through hot melt homogenization-ultrasound dispersion, and optimized by a quality-by-design (QbD) approach using Plackett-Burman design and Box-Behnken design. Plots were generated based on maximum desirability. Spherical, nanosized dispersions (<200 nm) with zeta potential ranging from -16.4 to -14.15 mV were observed. These nanoformulations demonstrated ~95% entrapment efficiency with around 5% drug loading. Stability tests revealed that the NLCs remained stable for 6 months under storage conditions at 4 °C. In vitro release studies indicated sustained release over 24 h, following Higuchi and Korsmeyer-Peppas models for NLCs and FA NLCs, respectively. Additionally, an in vitro pH-stat lipolysis model exhibited a nearly fivefold increase in bioaccessibility compared to drug-loaded suspensions. The DOC-ERL-loaded formulations exhibited dose- and time-dependent cytotoxicity, revealing synergism at a 1:3 molar ratio in MDA-MB-231 and 4T1 cells, with combination indices of 0.35 and 0.37, respectively. Co-treatment with DOC-ERL-loaded FA NLCs demonstrated synergistic anticancer effects in various in vitro assays.

Hyperreflective Ganglion Cell Layer Band in Gyrate Atrophy.

We have described the hyperreflective ganglion cell layer band (HGCB) in a series of cases of gyrate atrophy. Clinical fundus examination and multimodal imaging which included optical coherence tomography (OCT) was done in all cases. Four patients (one male, three female) were studied. In all four cases, a hyperreflective band was noted in the ganglion cell layer. In three patients, the band was continuous, and in one patient, the band was patchy. To conclude, HGCB is a novel OCT sign in gyrate atrophy and can be valuable in prognostication of disease. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Bone Marrow Aspirate Concentrate for Treatment of Primary Knee Osteoarthritis: A Prospective, Single-Center, Non-randomized Study with 2-Year Follow-Up.

Introduction: Knee osteoarthritis (OA) is a widespread, disabling condition with no intervention to fully restore cartilage or halt progression. Bone marrow aspirate concentrate (BMAC), an autologous product from bone marrow aspiration, has shown promise as a regenerative therapy due to its cell composition and chondrogenic effects. Our study aims to assess the functional outcomes, including pain, function, satisfaction, and complications post-BMAC injection in knee OA patients. Materials and Methods: In this prospective, single-center study, 63 patients with grade II-III knee OA (Kellgren-Lawrence (K-L) scale) unresponsive to conservative management underwent BMAC injection. The procedure involved bone marrow aspiration from the anterior iliac crest, processing to obtain a concentrate, followed by intra-articular injection. Patients were followed for 24 months, assessing outcomes using the Visual Analog Scale (VAS), International Knee Documentation Committee (IKDC) score, and MOCART 2.0 score. Results: The cohort, with a slight female predominance and predominantly aged 41-50 years, majorly comprised K-L grade III OA patients. BMAC treatment resulted in significant improvements in VAS pain scores, IKDC functional scores, and MOCART 2.0 scores over the 24-month follow-up. Conclusion: BMAC injection provides significant improvement in both pain and functional outcomes at mid-term follow-up in patients with mild-to-moderate OA of the knee. Further high-quality, adequately powered, multi-center, prospective, double-blinded, randomized controlled trials with longer follow-up are necessary to justify the routine clinical use of BMAC for treatment of patients suffering with knee OA.

Rare Extrapulmonary Tuberculosis: Covert symptoms and Diagnostic Dilemma.

Background: Pulmonary tuberculosis may result in haematogenous and lymphatic extension in case of failure of early detection, or immunocompromised status, leading to extrapulmonary tuberculosis. Rare sites of extrapulmonary tuberculosis include the gastrointestinal tract, musculoskeletal system, genital tract, middle ear and pericardium. Histopathological findings of macro-confluent granuloma with or without caseous necrosis, along with detection of acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining, and GeneXpert for detection of Mycobacterium tuberculosis DNA, are key in establishing a diagnosis of tuberculosis. Methodology: Biopsy-proven extrapulmonary granulomatous lesions were included in this study. Histopathological evaluation of all extrapulmonary biopsy specimens sent to the Department of Pathology were done for the presence of granuloma and necrosis, and ZN staining for AFB was done in all the cases of granulomatous lesions with or without the presence of necrosis. The same cases, with biopsy specimens sent in normal saline, were re-evaluated in a molecular laboratory with the help of GeneXpert MTB to detect the DNA of Mycobacterium tuberculosis. All biopsy specimens from extrapulmonary sites which were sent to the Department of Pathology were used for DNA extraction. Results: Out of the 10 cases of extrapulmonary granulomatous lesions, 8 showed caseous necrosis on microscopy, and 7 showed the presence of acid-fast bacilli on Ziehl-Neelsen staining. GeneXpert detected DNA of Mycobacterium tuberculosis in 9 cases. Conclusion: Extrapulmonary tuberculosis rarely occurs as primary, and mostly spreads from lung parenchyma via a haematogenous route. Tuberculosis of the gastrointestinal tract, peritoneum, lymph nodes, and solid viscera are together termed abdominal tuberculosis. Entities like tuberculosis of the pericardium and ear are extremely rare. Extrapulmonary tuberculosis should be a differential in cases of chronic non-responding cases with diagnostic dilemmas. To avoid diagnostic delay, in cases of high suspicion, one should go for biopsy along with ZN staining for diagnostic confirmation as this is cost-effective, followed by GeneXpert for Mycobacterium tuberculosis in highly suspected cases with absent caseous necrosis and negative ZN staining.

Bilateral Central serous chorioretinopathy in a case of surgically treated Optic Disc Pit maculopathy.

PURPOSE: To report occurrence of central serous chorioretinopathy(CSCR) which mimicked recurrence of ODP maculopathy in a young adult in whom surgery for the same had been done. METHODS: Clinical fundus examination and multimodal imaging which included optical coherence tomography(OCT) and fundus autofluorescence(FFA) was done. RESULTS: Patient had undergone surgery for ODP maculopathy. At 1 year follow up, there was recurrence of subretinal fluid at the macula. Fundus fluorescein angiography was done and the presence of ink blot pattern leakage clinched the diagnosis of CSCR, ruling out ODP maculopathy. CONCLUSION: CSCR is a great masquerade and correct diagnosis is very important to prevent permanent visual impairment. Subretinal fluid(SRF) associated with ODP must be examined carefully to rule out other pathologies like CSCR. Serous macular detachment after surgery for ODP maculopathy has been done, does not necessarily mean recurrence of the maculopathy. Other pathologies like CSCR should be ruled out. This case highlights the importance of multimodal imaging along with clinical signs in correct diagnosis and treatment of conditions with overlapping features like CSCR and ODP maculopathy.

Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits.

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-ß, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.

In situ hydrolysis of a carbophosphazene ligand leads to one-dimensional lanthanide coordination polymers. Synthesis, structure and dynamic magnetic studies.

An in situ hydrolysis of the P-Cl bonds of the carbophosphazene [{NC(NMe2)}2{NPCl2}] (LPCl2) in the presence of hydrated lanthanide(III) nitrates in a dichloromethane and methanol (2 : 1) solvent mixture afforded a series of novel 1D coordination polymers: [{Ln(LHPO2)3(NO3)2(CH3OH)(H2O)} (Cl)]n {where Ln(III) = Gd (1), Tb (2), Dy (3), or Er (4) and LHPO2 is the hydrolyzed carbophosphazene (LPCl2) ligand}. X-ray crystallographic analysis revealed that complexes 1-4 are isostructural and crystallized in the monoclinic crystal system having P21/c space group. The coordination polymers are formed because of the involvement of the geminal P(O)(OH) moieties of the carbophosphazene ligand. Each lanthanide(III) ion is 9-coordinate (9O) in a distorted muffin geometry. Magnetic measurements revealed that both DyIII and ErIII analogues exhibit field-induced single-molecule magnet (SMM) behavior at 0.8 kOe and 2.2 k Oe, respectively. At such dc fields, the dynamic magnetic susceptibility displays complex behavior with a triple magnetic relaxation contribution for 3, while two contributions were identified for 4. The observed static and dynamic magnetic behavior for complexes 1-4 were further rationalized with the aid of BS-DFT and CASSCF/SO-RASSI/SINGLE_ANISO calculations.

Eight-coordinate mono- and dinuclear Dy(III) complexes containing a rigid equatorial plane and an anisobidentate carboxylate ligand in the axial position: synthesis, structure and magnetism.

A rigid pentadentate chelating ligand (H2L) has been utilized to synthesize a series of octacoordinate mononuclear complexes, [Dy(L)(Ph3PO)(OOCR)] (where R = C6H5 (1), C(CH3)3 (2), CF3 (3)) and a dinuclear complex, [Dy2(L)2(Ph3PO)2{(OOC)2C6H4}] (4) based on the highly anisotropic Dy(III) ion. All the complexes were structurally characterized by single-crystal X-ray diffraction studies. The complexes were formed by the coordination action of the dianionic pentadentate ligand [L]2-, one phosphine oxide, and carboxylate ligands. DC and AC magnetic measurements were performed on 1-4. Complexes 1-4 show SMM behaviour, under zero DC field for 1 and 4, and under 500 Oe and 1000 Oe DC fields for 2 and 3 respectively, with thermally activated, Raman, and Raman and quantum tunnelling dominant relaxation mechanisms for 1 and 2, 3 and 4, respectively.

Efficacy of stromal vascular fraction for knee osteoarthritis: A prospective, single-centre, non-randomized study with 2 years follow-up.

BACKGROUND: Current osteoarthritis (OA) treatments focus on symptom relief without addressing the underlying disease process. In regenerative medicine, current treatments have limitations. In regenerative medicine, more research is needed for intra-articular stromal vascular fraction (SVF) injections in OA, including dosage optimization, long-term efficacy, safety, comparisons with other treatments, and mechanism exploration. AIM: To compare the efficacy of intra-articular SVF with corticosteroid (ICS) injections in patients with primary knee OA. METHODS: The study included 50 patients with Kellgren-Lawrence grades II and III OA. Patients were randomly assigned (1:1) to receive either a single intra-articular SVF injection (group A) or a single intra-articular ICS (triamcinolone) (group B) injection. Patients were followed up at 1, 3, 6, 12, and 24 months. Visual analog score (VAS) and International Knee Documentation Committee (IKDC) scores were administered before the procedure and at all follow-ups. The safety of SVF in terms of adverse and severe adverse events was recorded. Statistical analysis was performed with SPSS Version 26.0, IBM Corp, Chicago, IL, United States. RESULTS: Both groups had similar demographics and baseline clinical characteristics. Follow-up showed minor patient loss, resulting in 23 and 24 in groups A and B respectively. Group A experienced a notable reduction in pain, with VAS scores decreasing from 7.7 to 2.4 over 24 months, compared to a minor reduction from 7.8 to 6.2 in Group B. This difference in pain reduction in group A was statistically significant from the third month onwards. Additionally, Group A showed significant improvements in knee functionality, with IKDC scores rising from 33.4 to 83.10, whereas Group B saw a modest increase from 36.7 to 45.16. The improvement in Group A was statistically significant from 6 months and maintained through 24 months. CONCLUSION: Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA. More adequately powered, multi-center, double-blinded, randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Electrical noise spectroscopy of magnons in a quantum Hall ferromagnet.

Collective spin-wave excitations, magnons, are promising quasi-particles for next-generation spintronics devices, including platforms for information transfer. In a quantum Hall ferromagnets, detection of these charge-neutral excitations relies on the conversion of magnons into electrical signals in the form of excess electrons and holes, but if the excess electron and holes are equal, detecting an electrical signal is challenging. In this work, we overcome this shortcoming by measuring the electrical noise generated by magnons. We use the symmetry-broken quantum Hall ferromagnet of the zeroth Landau level in graphene to launch magnons. Absorption of these magnons creates excess noise above the Zeeman energy and remains finite even when the average electrical signal is zero. Moreover, we formulate a theoretical model in which the noise is produced by equilibration between edge channels and propagating magnons. Our model also allows us to pinpoint the regime of ballistic magnon transport in our device.

Metal-free platforms for molecular thin films as high-performance supercapacitors.

Controlling chemical functionalization and achieving stable electrode-molecule interfaces for high-performance electrochemical energy storage applications remain challenging tasks. Herein, we present a simple, controllable, scalable, and versatile electrochemical modification approach of graphite rods (GRs) extracted from low-cost Eveready cells that were covalently modified with anthracene oligomers. The anthracene oligomers with a total layer thickness of ∼24 nm on the GR electrode yield a remarkable specific capacitance of ∼670 F g-1 with good galvanostatic charge-discharge cycling stability (10 000) recorded in 1 M H2SO4 electrolyte. Such a boost in capacitance is attributed mainly to two contributions: (i) an electrical double-layer at the anthracene oligomer/GR/electrolyte interfaces, and (ii) the proton-coupled electron transfer (PCET) reaction, which ensures a substantial faradaic contribution to the total capacitance. Due to the higher conductivity of the anthracene films, it possesses more azo groups (-N[double bond, length as m-dash]N-) during the electrochemical growth of the oligomer films compared to pyrene and naphthalene oligomers, which is key to PCET reactions. AC-based electrical studies unravel the in-depth charge interfacial electrical behavior of anthracene-grafted electrodes. Asymmetrical solid-state supercapacitor devices were made using anthracene-modified biomass-derived porous carbon, which showed improved performance with a specific capacitance of ∼155 F g-1 at 2 A g-1 with an energy density of 5.8 W h kg-1 at a high-power density of 2010 W kg-1 and powered LED lighting for a longer period. The present work provides a promising metal-free approach in developing organic thin-film hybrid capacitors.

Identification and Analysis of Atrial-Bronchial-Abdominal Disharmony in Patients with Isomeric Atrial Appendages.

Ideally, the morphology of atrial appendages should solely be used to identify and differentiate patients with isomeric right and left atrial appendages. However, in clinical practice, the segregation is often indirectly based on the arrangement of thoraco-abdominal structures. The correlation between thoraco-abdominal arrangement and atrial appendages, however, is imperfect. In this study, we sought to clarify the cardiovascular malformations in patients with isomeric atrial appendages with an emphasis on atrial-thoracic-abdominal disharmony. A retrospective review of all patients who underwent cardiac CT angiography between January 2014 and June 2023 and identified to have isomeric atrial appendages was performed. Of the 366 cases (median age: 2 years [interquartile range: 11 months-7 years]), 247 (67.5%) patients had isomeric right atrial appendages while 119 (32.5%) patients had isomeric left atrial appendages. In 316 (86.3%) patients, the thoraco-abdominal arrangement was as per atrial appendage morphology while the remaining 50 (13.6%) patients had disharmonious patterns. Compared to isomeric left atrial appendages, the disharmonious pattern was more frequent with isomeric right atrial appendages (5.9% vs. 17.4%; p 0.003). Irrespective of the type of isomerism, disharmony was mostly confined to the level of the abdomen. Not all patients with isomeric atrial appendages have a harmonious thoraco-abdominal arrangement. The atrial-bronchial-abdominal disharmony is more frequent with isomeric right atrial appendages and is mostly present at the level of the abdomen. A detailed sequential segmental analysis with an independent description of each organ system is, therefore, essential for the complete evaluation of patients with isomeric atrial appendages.

Immunoinhibitory effects of anti-tuberculosis therapy induce the host vulnerability to tuberculosis recurrence.

The host immune responses play a pivotal role in the establishment of long-term memory responses, which effectively aids in infection clearance. However, the prevailing anti-tuberculosis therapy, while aiming to combat tuberculosis (TB), also debilitates innate and adaptive immune components of the host. In this study, we explored how the front-line anti-TB drugs impact the host immune cells by modulating multiple signaling pathways and subsequently leading to disease relapse. Administration of these drugs led to a reduction in innate immune activation and also the cytokines required to trigger protective T cell responses. Moreover, these drugs led to activation-induced cell death in the mycobacterial-specific T cell leading to a reduced killing capacity. Furthermore, these drugs stalled the T cell differentiation into memory subsets by modulating the activation of STAT3, STAT4, FOXO1, and NFκB transcription factors and hampering the Th1 and Th17-mediated long-term host protective memory responses. These findings suggest the urgent need to augment directly observed treatment, short-course (DOTS) therapy with immunomodulatory agents to mitigate the adverse effects linked to the treatment.IMPORTANCEAs a central component of TB eradication initiatives, directly observed treatment, short-course (DOTS) therapy imparts immune-dampening effects during the course of treatment. This approach undermines the host immune system by delaying the activation process and lowering the immune response. In our investigation, we have unveiled the impact of DOTS on specific immune cell populations. Notably, the signaling pathways involving STAT3 and STAT4 critical for memory responses and NFκß associated with pro-inflammation were substantially declined due to the therapy. Consequently, these drugs exhibit limited effectiveness in preventing recurrence of the disease. These observations highlight the imperative integration of immunomodulators to manage TB infection.