Sex-dependent differences in macaque brain mitochondria.

Mitochondrial bioenergetics in females and males is different. Whether mitochondria from male and female brains display differences in mitochondrial enzymes is unknown. We measured the function of mitochondrial complexes from the brains of male and female macaques (Macaca mulatta). Cerebral tissue of macaques males exhibit elevated content and activity of mitochondrial complex I (NADH:ubiquinone oxidoreductase) and activity of complex II compared to females. No significant differences between sexes were found in the content of α-ketoglutarate dehydrogenase and activities of cytochrome c oxidase and F1Fo ATPase. Our results, underscore the need for further investigations to elucidate sex-related mitochondrial distinctions in humans.

Particle-ozone complex pollution under diverse synoptic weather patterns in the Yangtze River Delta region: Synergistic relationships and the effects of meteorology and chemical compositions.

There is considerable academic interest in the particle-ozone synergistic relationship (PO) between fine particulate matter (PM2.5) and ozone (O3). Using various synoptic weather patterns (SWPs), we quantitatively assessed the variations in the PO, which is relevant to formulating policies aimed at controlling complex pollution in the air. First, based on one-year sampling data from March 2018 to February 2019, the SWPs classification of the Yangtze River Delta (YRD) was conducted using the sum-of-squares technique (SS). Five dominant SWPs can be found in the YRD region, including the Aleutian low under SWP1 (occurring 45 % of the year), a tropical cyclone under SWP2 (21 %), the tropical cyclone and western Pacific Subtropical High (WPSH) under SWP3 (15.4 %), the WPSH under SWP4 (6.9 %), and a continental high pressure under SWP5 (3.1 %). The phenomenon of a "seesaw" between PM2.5 and O3 concentrations exhibited significant spatial heterogeneity, which was influenced by meteorological mechanisms. Second, the multi-linear regression (MLR) model and the partial correlation (PCOR) analysis were employed to quantify the effects of dominant components and meteorological factors on the PO. Meteorological variables could collectively explain only 33.0 % of the PM2.5 variations, but 58.0 % for O3. O3 promoted each other with low concentrations of PM2.5 but was inhibited by high concentrations of PM2.5. High relative humidity (RH) was conducive to the generation of PM2.5 secondary components and enhanced the radiative effects of aerosols and the negative correlation of PO. In addition, attention should be paid to assessing the combined effects of precursor levels, weather, and chemical reactions on the particle-ozone complex pollution. The control of O3 pollutants should be intensified in summer, while the focus should be on reducing PM2.5 pollutants in winter. Prevention and control measures need to reflect the differences in weather conditions and pollution characteristics, with a focus on RH and secondary components of PM2.5.

Transmembrane protein TMEM230, regulator of metalloproteins and motor proteins in gliomas and gliosis.

Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis.

Single-cell transcriptomic analysis to identify endomembrane regulation of metalloproteins and motor proteins in autoimmunity.

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.

Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.

We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.

Optimizing Treatment for Carbapenem-Resistant Acinetobacter baumannii Complex Infections: A Review of Current Evidence.

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively.

Bridging the gap to meet complex needs: an intersectoral action well supported by appropriate policies and governance.

Many people face problems about physical, mental, and social dimensions of health, and may have complex needs. They often experience a mismatch between their needs and the ability of the healthcare system to meet them, resulting in under- or overutilization of the healthcare system. On one hand, improving access to community-based primary healthcare for hard-to-reach populations should bring all healthcare and social services to one point of contact, near the community. On the other hand, better addressing the unmet needs of people who overuse healthcare services calls for integrated care among providers across all settings and sectors. In either case, intersectoral action between healthcare and social professionals and resources remains central to bringing care closer to the people and the community, enhancing equitable access, and improving health status. However, efforts to implement integrated care are unevenly weighted toward clinical and professional strategies (micro level), which could jeopardize our ability to implement and sustain integrated care. The development of appropriate policies and governance mechanisms (macro level) is essential to break down silos, promote a coherent intersectoral action, and improve health equity.

Complex Hand Reconstruction using a Novel Two-stage Temporary Ectopic Implantation of the Contralateral Upper Limb.

Ectopic transplantation of the hand remains a rare, innovative yet valuable operation in select cases of trauma and amputation. We aim to describe a novel technique of complex hand reconstruction using a two-stage ectopic implantation of the contralateral upper limb. A male patient with a near complete avulsion amputation of the right upper limb at the level of the mid-forearm and a crushing injury to his left hand was admitted after a farming accident. The right palm was ectopically transplanted to the left lower limb and both upper limbs underwent debridement with vacuum assisted dressings (VACs). There was eventual dieback of the left thumb, ring and little finger with a large palmar soft tissue defect that was eventually reconstructed using segments of the ectopically transplanted limb in two separate operations. The patient made an uneventful postoperative recovery and managed to regain protective sensation and gross motor function of his reconstructed hand.

Harnessing Solar Power for Oxidation of Organic Compounds by Re(I)Dipyrrinato Complexes.

Metal dipyrrinato complexes of 4d and 5d metals have distinctive features such as high absorption coefficients in the visible section and room temperature phosphorescence in the red region. This work demonstrates the light-assisted oxidation of organic compounds employing rhenium(I)dipyrrinato complexes as catalysts. The heavy atom effect in rhenium(I)dipyrrinato complexes leads to the formation of long-lived triplet excited states, and these complexes can generate singlet oxygen in excellent yields (up to 84%). A method was developed for photocatalytic aerobic oxidation of sulfides and amines using only 0.05 mol % and 0.025 mol % of the rhenium(I)dipyrrinato complexes, respectively. The method is efficient, and within 2h, a variety of substrates were oxidized to produce sulfoxides and imines in high yields (up to 97%). rhenium(I)dipyrrinato complexes work very well both in visible light and sunlight, making them promising candidates for photocatalytic applications.

Elimination of GGTA1, CMAH, ß4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions.

BACKGROUND: Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles. METHODS: Thus, we generate a 4-gene (GGTA1, CMAH, ß4GalNT2, and CIITA) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously. RESULTS: We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3 months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment. CONCLUSIONS: 4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.

Structure and Function of the Glycosylphosphatidylinositol Transamidase, a Transmembrane Complex Catalyzing GPI Anchoring of Proteins.

Glycosylphosphatidylinositol (GPI) anchoring of proteins is a ubiquitous posttranslational modification in eukaryotic cells. GPI-anchored proteins (GPI-APs) play critical roles in enzymatic, signaling, regulatory, and adhesion processes. Over 20 enzymes are involved in GPI synthesis, attachment to client proteins, and remodeling after attachment. The GPI transamidase (GPI-T), a large complex located in the endoplasmic reticulum membrane, catalyzes the attachment step by replacing a C-terminal signal peptide of proproteins with GPI. In the last three decades, extensive research has been conducted on the mechanism of the transamidation reaction, the components of the GPI-T complex, the role of each subunit, and the substrate specificity. Two recent studies have reported the three-dimensional architecture of GPI-T, which represent the first structures of the pathway. The structures provide detailed mechanisms for assembly that rationalizes previous biochemical results and subunit-dependent stability data. While the structural data confirm the catalytic role of PIGK, which likely uses a caspase-like mechanism to cleave the proproteins, they suggest that unlike previously proposed, GPAA1 is not a catalytic subunit. The structures also reveal a shared cavity for GPI binding. Somewhat unexpectedly, PIGT, a single-pass membrane protein, plays a crucial role in GPI recognition. Consistent with the assembly mechanisms and the active site architecture, most of the disease mutations occur near the active site or the subunit interfaces. Finally, the catalytic dyad is located ~22 Å away from the membrane interface of the GPI-binding site, and this architecture may confer substrate specificity through topological matching between the substrates and the elongated active site. The research conducted thus far sheds light on the intricate processes involved in GPI anchoring and paves the way for further mechanistic studies of GPI-T.

Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.

The present work delves into the enigmatic world of mitochondrial alpha-keto acid dehydrogenase complexes discussing their metabolic significance, enzymatic operation, moonlighting activities, and pathological relevance with links to underlying structural features. This ubiquitous family of related but diverse multienzyme complexes is involved in carbohydrate metabolism (pyruvate dehydrogenase complex), the citric acid cycle (α-ketoglutarate dehydrogenase complex), and amino acid catabolism (branched-chain α-keto acid dehydrogenase complex, α-ketoadipate dehydrogenase complex); the complexes all function at strategic points and also participate in regulation in these metabolic pathways. These systems are among the largest multienzyme complexes with at times more than 100 protein chains and weights ranging up to ~10 million Daltons. Our chapter offers a wealth of up-to-date information on these multienzyme complexes for a comprehensive understanding of their significance in health and disease.

Formation of a Decanuclear Organometallic Dysprosium Complex via a Radical-Radical Cross-Coupling Reaction.

Over the years, polynuclear cyclic or torus complexes have attracted increasing interest due to their unique metal topologies and properties. However, the isolation of polynuclear cyclic organometallic complexes is extremely challenging due to their inherent reactivity, which stems from the labile and reactive metal-carbon bonds. In this study, the pyrazine ligand undergoes a radical-radical cross-coupling reaction leading to the formation of a decanuclear [(Cp*)20Dy10(L1)10]·12(C7H8) (1; where L1 = anion of 2-prop-2-enyl-2H-pyrazine) complex, where all DyIII metal centers are bridged by the anionic L1 ligand. Amongst the family of polynuclear Ln organometallic complexes bearing CpR2Lnx units, 1 features the highest nuclearity obtained to date. In-depth computational studies were conducted to elucidate the proposed reaction mechanism and formation of L1, while probing of the magnetic properties of 1, revealed slow magnetic relaxation upon application of a static dc field.

Sensing the squeeze: nuclear mechanotransduction in health and disease.

The nucleus not only is a repository for DNA but also a center of cellular and nuclear mechanotransduction. From nuclear deformation to the interplay between mechanosensing components and genetic control, the nucleus is poised at the nexus of mechanical forces and cellular function. Understanding the stresses acting on the nucleus, its mechanical properties, and their effects on gene expression is therefore crucial to appreciate its mechanosensitive function. In this review, we examine many elements of nuclear mechanotransduction, and discuss the repercussions on the health of cells and states of illness. By describing the processes that underlie nuclear mechanosensation and analyzing its effects on gene regulation, the review endeavors to open new avenues for studying nuclear mechanics in physiology and diseases.

A retrospective cross-sectional study of risk factors for communicable disease diagnoses among refugees in mainland Greek camps, 2016-2017.

Communicable disease risk is high in refugee camps and reception centers. To better understand the risks for communicable disease diagnoses among refugees and asylum seekers, this study assesses individual- and camp-level risk factors among individuals utilizing Médecins du Monde clinics in four large refugee camps-Elliniko, Malakasa, Koutsochero, and Raidestos-on mainland Greece between July 2016 and May 2017. Descriptive statistics are reported for the demographic characteristics of the study population and for communicable disease burdens within the four camps-Elliniko, Malakasa, Raidestos, and Koutsochero. A hierarchical generalized linear model was used to assess risk factors for communicable disease diagnoses while accounting for individual-level clustering. This study shows marginal patterns in risk factors for communicable disease. Males had marginally higher risk of communicable disease diagnosis than females (OR = 1.12; 95% CI 0.97-1.29), and increased age was more protective against communicable disease for females (OR = 0.957; 95% CI 0.953-0.961) than for males (OR = 0.963; 95% CI 0.959-0.967). Communicable disease risk was significantly different between camps, with Elliniko (OR = 1.58; 95% CI 1.40-1.79) and Malakasa (OR = 1.43; 95% CI 1.25-1.63) having higher odds of communicable disease than Raidestos. The demographic and epidemiologic profiles of displaced populations differ across settings, and epidemiologic baselines for displaced populations are fundamental to evidence-informed provision of humanitarian aid. Further, while influences and risks for negative health outcomes in complex emergencies are broadly, the causal mechanisms that underpin these relationships are not as well understood. Both practitioners and researchers should engage with further research to elucidate the mechanisms through which these risks operate among displaced populations, including multilevel analyses.

Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing: From Sequence Data to Resistance Profiles.

Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many first- and second-line anti-tuberculosis drugs. However, bioinformatic pipelines and mutation catalogs to predict antimicrobial resistances in MTBC isolates are often customized and detailed protocols are difficult to access. Here, we provide a step-by-step workflow for the processing and interpretation of short-read sequencing data and give an overview of available analysis pipelines.

Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing.

Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in many countries. WGS protocols usually start with the preparation of a DNA-library: the critical first step in the process. A DNA-library represents the genomic content of a DNA sample and consists of unique short DNA fragments. Although available DNA-library protocols come with manufacturer instructions, details of the entire process, including quality controls, instrument parameters, and run evaluations, often need to be developed and customized by each laboratory to implement WGS technology effectively. Here, we provide a detailed workflow for a DNA-library preparation based on an adapted Illumina protocol optimized for the reduction of reagent costs.

Intergenerational associations between childhood maltreatment, post-traumatic stress symptoms, and chronic pain in young adult offspring and their parents.

Findings have revealed a strong link between exposure to child maltreatment (CM) and later chronic pain. Concurrently, other findings have been grounded in the understanding that CM consequences may not end with the exposed individual, rather, they extend to their offspring. However, little is known regarding the possible intergenerational transmission of chronic pain following CM. This study examines whether chronic pain among parents and their young adult offspring may be associated with parental exposure to CM. Three hundred ninety-three parent-offspring dyads (parents' mean age = 58, SD = 5.91 years; offspring's mean age = 27, SD = 3.91 years) completed self-report questionnaires, assessing CM (CTQ), posttraumatic stress (PTS) and disturbances in self-organisation (DSO) symptoms (ITQ), and chronic pain. CM was associated with chronic pain mediated by DSO symptoms among parents (indirect effect = 0.77; p = 0.007) and PTS symptoms among offspring (indirect effect = 0.285; p = 0.005). Offspring chronic pain was significantly associated with parental CM through two intergenerational paths: the mediation of parents' DSO symptoms and chronic pain (indirect effect = 0.298; p = 0.011), and through parents' PTS symptoms and offspring's PTS symptoms (indirect effect = 0.077; p = 0.004). This study's findings support the relevance of the intergenerational transmission of chronic pain following parental exposure to CM. Furthermore, the findings reveal complex PTS symptoms as a possible underlying mechanism for the intergenerational associations of chronic pain following CM.

Evaluation of Antimicrobial Susceptibility and Resistance Patterns of Treponema denticola Isolated From Periodontal Disease: An In Vitro Study.

Background Periodontal disease poses a significant oral health challenge, involving inflammatory conditions impacting tooth-supporting structures. Treponema denticola, a "red complex" organism, plays a crucial role in periodontal pathogenesis, forming biofilms in subgingival environments and contributing to dysbiosis. Antimicrobial therapy is pivotal in managing periodontal disease, requiring a nuanced understanding of susceptibility patterns exhibited by key pathogens like T. denticola. Aims and objectives This study aims to investigate the antimicrobial susceptibility and resistance profiles of Treponema denticola, a prominent bacterium in periodontal disease, by examining its responses to various antimicrobial agents commonly used in periodontal therapy. Methodology Plaque samples were meticulously collected from individuals diagnosed with periodontal disease to ensure a diverse representation of the oral microbiome. All the samples were cultured, and red complex bacteria were isolated under anaerobic culture. Treponema denticola isolates were cultured from these samples under anaerobic conditions, and molecular techniques were employed for species identification. A comprehensive panel of antimicrobial agents was selected to assess the response of Treponema denticola. In vitro antimicrobial susceptibility testing (AST) was conducted using the antimicrobial gradient method, employing a hybrid approach combining elements of disk-diffusion and dilution methods. Results Treponema denticola had exhibited resistance to metronidazole, a commonly used antibiotic effective against anaerobic bacteria, emphasizing limitations in its applicability. However, the bacterium displayed sensitivity to tetracycline, imipenem, cefoperazone, chloramphenicol, clindamycin, and moxifloxacin, offering diverse therapeutic options. The antimicrobial gradient strip test provided detailed minimum inhibitory concentration (MIC) values, contributing to a nuanced understanding of susceptibility and resistance patterns. Conclusion This study significantly advances our understanding of Treponema denticola's antimicrobial susceptibility and resistance profiles in the context of periodontal disease. The findings underscore the importance of tailored treatment strategies and contribute to broader efforts in antimicrobial stewardship, aligning with global initiatives to combat antibiotic resistance. This research lays the foundation for more effective and personalized approaches to periodontal care, emphasizing the intricate microbial dynamics associated with periodontal health and disease.