Anorectal lymphogranuloma venereum (LGV) can mimic rectal malignancy, but diagnosis may be challenging when LGV-specific serovar testing is unavailable. A 26-year-old man who has sex with men presented with hematochezia and increased bowel movement frequency. Colonoscopy revealed a large deep rectal ulcer with mucopurulent exudate, and pelvic magnetic resonance imaging showed rectal wall thickening with regional lymphadenopathy, raising concern for rectal cancer. Histopathology showed inflammatory changes without malignancy. Rectal secretion testing was positive for Chlamydia trachomatis RNA, and the patient was clinically diagnosed with probable anorectal LGV. Oral doxycycline 100 mg twice daily for 21 days led to marked ulcer regression at 3 weeks and near-complete mucosal healing by 6 weeks. This case highlights the importance of considering sexually transmitted proctitis in young men who have sex with men patients with atypical rectal ulcers.

Complete responses in metastatic pancreatic adenosquamous carcinoma (ASCP) are extremely rare and carbohydrate antigen 19-9 (CA 19-9) interpretation is difficult during cholestasis. A 65-year-old man underwent Whipple procedure on 29 May 2025; pathology confirmed ASCP (pT3 pN2, R0). Contrast-enhanced magnetic resonance imaging (MRI) on 26 June 2025 showed 11 liver lesions interpreted as metastases. Treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) began on 7 July 2025. From cycle 2, high-dose intravenous vitamin C, doxycycline and later azithromycin were added by the patient and author as off-label home measures, without efficacy claims. After three cycles, follow-up MRI showed complete radiological regression of the hepatic lesions; MRI around the sixth cycle confirmed complete radiological response. Chemotherapy stopped after six cycles. In late September 2025, cholestasis and CA 19-9 rise were initially suspected as recurrence; after ursodeoxycholic acid, CA 19-9 decreased and normalized by 10 January 2026. Follow-up MRI on 20 February 2026 showed no visible hepatic lesions.

Lyme disease may involve the heart during early dissemination and most commonly produces atrioventricular (AV) conduction abnormalities. PR interval prolongation, therefore, frequently guides clinical suspicion and management. We describe a previously healthy man who presented with seizure-like activity, aborted cardiac arrest, transient atrial fibrillation, and cardiac magnetic resonance findings consistent with acute myocarditis, although AV conduction remained normal. Serologic testing subsequently confirmed Lyme carditis. The patient recovered completely with oral doxycycline. This case illustrates that electrical instability may occur despite preserved PR intervals and reinforces the need for suspicion in patients with compatible systemic features.

Black soldier fly larvae (BSFL) bioconversion of doxycycline-contaminated hen manure raises concerns about antibiotic resistance gene (ARG) transmission. Although core microbiota in gut may participate in ARG dynamics, the relative contributions of microbiota from manure and baseline larval gut to the BSFL gut resistome remain unclear. Using metagenomics, amplicon sequencing, and cultivable bacteria analysis, we found that: (1) Providencia, Klebsiella, Enterococcus, and Escherichia-Shigella dominated the BSFL gut and served as primary ARG hosts; (2) Fecal filtrate intervention drastically altered gut microbiota and ARG profiles, suppressing Klebsiella (by 95.56%) and Escherichia-Shigella (to < 0.5%) while enriching Providencia (3.53 fold increase) and Enterococcus, with increased ARGs such as tet(59) and qnrD1. Long-read metagenomic analysis indicated that viable manure-borne bacteria, rather than cell-free fecal filtrate, delivered structurally intact ARG-MGE units as key carrier of mobile resistance cassettes; (3) Source tracking (FEAST) assigned the majority of ARBs (> 90%) and their ARGs in the BSFL gut to the baseline BSFL gut source, with manure-derived ARBs contributing 4.80%. Culture-based 16S rRNA gene homology provided evidence consistent with possible manure-to-gut transfer of selected Escherichia-Shigella and Enterococcus. The BSFL gut resistome was more strongly associated with the baseline BSFL microbiota than with manure, but manure still represented a detectable source of ARB and ARG introduction. FEAST source assignments should be interpreted as composition-based bioinformatic estimates rather than definitive proof of origin, due to lack of direct functional tracing. These findings have critical implications for assessing the ecological safety of BSFL-based waste valorization.

Tristetraprolin (TTP/ZFP36) regulates mRNA expression; however, its target genes in lung cancer remain unclear. Using a CRISPR/Cas9-engineered doxycycline-inducible TTP knock-in model in H460 cells, we investigated the function of TTP in lung cancer cells. Induced TTP expression suppressed clonogenicity, spheroid growth, proliferation, invasion, and migration. Transcriptomic analyses integrated with public lung adenocarcinoma datasets identified glucosaminyl (N-acetyl) transferase 3 (GCNT3) as a key effector of TTP in cancer progression. Mechanistic analyses indicated direct TTP binding to GCNT3, reducing its expression. GCNT3 knockdown attenuated invasion and migration, and GCNT3 re-expression in TTP-induced cells restored and further enhanced these malignant behaviors, establishing a functional relationship between TTP and GCNT3. Transient TTP expression in H1299 cells also reduced GCNT3 levels. These findings identify GCNT3 as a direct TTP target that contributes to malignant behaviors in lung cancer cells, providing insights into post-transcriptional regulation of tumor progression.

Brazilian spotted fever, caused by Rickettsia rickettsii, is a life-threatening tick-borne disease endemic to southeastern Brazil and is associated with high mortality when treatment is delayed. Central nervous system involvement poses a particular diagnostic challenge because of nonspecific early symptoms and frequent misdiagnosis as dengue or leptospirosis. We report a case illustrating characteristic neuroimaging findings and therapeutic considerations in rickettsial encephalitis. We describe the clinical course, cerebrospinal fluid (CSF) findings, magnetic resonance imaging (MRI) findings, serologic results, and treatment response in a 23-year-old man who presented with febrile encephalopathy in an endemic region of Brazil. The patient had a five-day history of fever, erythematous macules, and progressive encephalopathy. CSF analysis showed elevated protein and lymphocytic pleocytosis. MRI showed T2/fluid-attenuated inversion recovery hyperintensities with restricted diffusion involving the bilateral corticospinal tracts and the splenium of the corpus callosum, forming a "boomerang" pattern. Clinical improvement followed initiation of empirical doxycycline and pulse methylprednisolone. Serologic testing supported the diagnosis of R. rickettsii infection with a positive immunoglobulin M titer of 1:512. Follow-up MRI showed near-complete lesion resolution at 4 months, with a residual splenial lesion persisting at 18 months. This case illustrates the importance of recognizing characteristic MRI patterns, including the "starry sky" and "boomerang" signs, as diagnostic clues in rickettsial encephalitis, even when the classic triad is incomplete. Early empirical doxycycline remains critical for neurologic outcomes, and adjunctive corticosteroids may have a role in selected cases when immune-mediated central nervous system injury is suspected.

Tuberculous meningitis (TBM) is a severe and often fatal form of extrapulmonary tuberculosis. We describe a case in which the initial cerebrospinal fluid (CSF) analysis showed no specific abnormalities, but a diagnosis was established after repeat CSF evaluation. A 41-year-old female presented with a 10-day history of persistent fever and headache. Initial CSF analysis demonstrated an opening pressure of 150 mmH2O, a white blood cell (WBC) count of 10/μL, a glucose level of 50 mg/dL, and a protein level of 31.4 mg/dL. Despite treatment with an antiviral agent and doxycycline, her symptoms did not improve. A repeat CSF analysis demonstrated an opening pressure of 120 mmH2O, an elevated WBC count of 140/μL (55% lymphocytes), a glucose level of 52 mg/dL, and an elevated protein level of 201.6 mg/dL, which was highly suggestive of TBM. This case highlights the importance of repeat CSF analysis based on clinical judgment when diagnosing TBM.

Activation of redox-sensitive signal transduction cascades is an increasingly appreciated mechanism of exercise adaptation in skeletal muscle. Aging and disease are associated with altered redox homeostasis, potentially altering redox responses to muscle contraction, and adaptations to exercise. It is unclear how chronic steady-state changes in redox homeostasis affect contraction-induced signaling cascades. Here we use a novel model of inducible superoxide dismutase 2 knockdown (iSOD2 KD) in skeletal muscle to test how chronic mitochondrial redox perturbations affect subsequent signaling responses to acute fatiguing muscle contraction. After a 12-week doxycycline treatment to knock down SOD2, littermate controls (CON) and iSOD2 KD animals underwent a single acute fatiguing contractile stimulus of the right hindlimb. Muscle tissue was collected immediately after or 3 hours after completion of the stimulus followed by redox proteomic and transcriptomic analysis, respectively, and compared to naïve unstimulated controls of each genotype. iSOD2 KD led to decreased protein expression of several key iron-sulfur cluster biosynthesis proteins and increased reversible thiol oxidation of proteins in the mitochondrial compartment in response to muscle contraction. The transcriptomic response to contraction in KD shows activation of apoptosis, oxidative stress, and inflammatory pathways and no significant perturbation in controls. Controls show pathway activation of insulin signaling and glucose metabolism, calcium signaling, and energy stress signaling processes compared to no activation in KD muscle. These results indicate that chronic mitochondrial redox stress shifts acute signaling responses away from metabolic signaling pathways and toward oxidative stress and apoptotic signaling processes which may lead to pathological or maladaptive signaling responses over time.

The dual-specificity tyrosine-regulated kinase DYRK1B is frequently expressed at elevated levels in solid tumors and has been implicated in cancer cell survival, therapy resistance, and cell cycle arrest. While DYRK1B is best known for maintaining quiescence, its broader impact on cancer cell phenotypic plasticity remains incompletely understood. Using a doxycycline-inducible A549 lung adenocarcinoma model, we show that sustained overexpression of catalytically active DYRK1B induces senescence-related phenotypic changes. DYRK1B overexpression led to increased senescence-associated β-galactosidase activity, cell enlargement and granularity, and robust induction of the cyclin-dependent kinase inhibitor p21[Waf1/Cip1]. RNA-sequencing revealed extensive transcriptional reprogramming, with strong overlap to established cellular senescence signatures. Gene set enrichment analysis further identified suppression of E2F target genes, consistent with durable proliferation arrest. Senescence-associated secretory phenotype (SASP) components, including PAI-1 (SERPINE1), CCL2, IGFBP7, were significantly upregulated at both mRNA and protein levels. These effects were not observed with a kinase-impaired DYRK1B mutant. Gene set enrichment analysis further identified enrichment of epithelial-mesenchymal transition (EMT) transcriptional programs, consistent with EMT-associated phenotypic effects of DYRK1B overexpression that we have reported previously. These findings identify DYRK1B as an inducer of senescence-like transcriptional and secretory programs when expressed at elevated levels in A549 lung cancer cells in vitro. Although currently speculative and awaiting in vivo validation, we hypothesize that DYRK1B-induced senescence might contribute to tumor cell persistence and therapy resistance, highlighting DYRK1B as a potential target for modulating cancer cell plasticity and senescence-associated phenotypes.

Doxycycline is a widely used antibiotic for commonly encountered infections and is generally well tolerated. However, it is associated with rare, drug-induced severe thrombocytopenia, which, if not promptly recognised and managed, could prove fatal. We present a case of doxycycline-induced severe thrombocytopenia in a 63-year-old man with a background of type 2 diabetes mellitus, left ventricular systolic dysfunction, and hypothyroidism. The platelet count dropped to a critical level of 6 x 10[9]/L following a one-week course of doxycycline, which improved with drug withdrawal, platelet transfusions, and a course of high-dose steroid therapy over three weeks. This was evidenced by a Naranjo Adverse Drug Reaction Probability Scale score of 8/13, which is the upper limit for a probable adverse drug reaction. This rare but life-threatening side effect of doxycycline highlights the need for a follow-up blood test shortly after commencing therapy for early detection and prompt management.

Brucellosis is a multisystem zoonosis that can mimic complicated bacterial infection in children. A 10-year-old girl presented with prolonged high-grade fever, jaundice, abdominal pain, anorexia and weight loss. The initial syndrome was managed empirically as an undifferentiated complicated bacterial illness because enteric fever and a hepatobiliary or intra-abdominal source were considered. CRP was 333.2 mg/L and total/direct bilirubin 7.24/5.21 mg/dL despite only mild aminotransferase elevation; ultrasonography showed hepatomegaly and nonspecific gallbladder-wall edema without biliary dilatation or focal lesions. CRP peaked at 407.1 mg/L and began falling during meropenem-linezolid therapy before Brucella-directed treatment, so biomarker response was not used diagnostically. Re-taking the history revealed daily consumption of unboiled dairy milk for several months. On hospital day 6, doxycycline, rifampicin and gentamicin were started simultaneously, with discontinuation of meropenem and linezolid. Brucella serology was concordant: a laboratory-reported agglutination result labelled B. melitensis was reactive at 1:80 and later EIA showed strongly positive IgM and IgG, but neither test established species identity and culture/PCR confirmation was not obtained. Fever resolved by hospital day 14. At immediate post-treatment follow-up on 8 September 2026, she remained clinically well; weight had increased from 19 to 20 kg, CRP was 1.2 mg/L, total/direct bilirubin 0.8/0.2 mg/dL, AST/ALT 34/43 IU/L and alkaline phosphatase 417 U/L (within a published pediatric reference interval), with renal function within the laboratory reference range. Hemoglobin had improved to 7.8 g/dL with persistent microcytosis, before oral iron supplementation was initiated. The diagnosis is therefore best regarded as serologically supported pediatric brucellosis rather than microbiologically confirmed disease.

The presence of antibiotic residues in poultry meat poses a growing risk of non-compliance with maximum residue limits under international food safety regulations. However, existing screening methods to detect antibiotic overuse rely mainly on LC-MS with dispersive solid-phase extraction (dSPE) clean-up using instrumentation and sorbents that are economically inaccessible to many food-safety laboratories in resource-limited countries where such monitoring is most needed. This work develops and validates a sorbent-free, HPLC-UV multiclass screening procedure for six antibiotic residues (sulfadiazine, trimethoprim, ciprofloxacin, enrofloxacin, sulfamethoxazole and doxycycline) in chicken meat samples prior to confirmatory testing by the LC-MS technique. Three integrated methodological milestones were achieved in this work. First, mechanistic retention-time modeling equations were applied to optimize a gradient HPLC-UV separation for the studied compounds based on only six scouting runs without trial-and-error effort. Second, the extraction procedure was optimized using the Plackett-Burman screening, followed by Box-Behnken response surface design, yielding a modified QuEChERS extraction method, eliminating the dSPE step. Third, a salt-assisted liquid-liquid microextraction (SALLME) preconcentration step for the recovered analytes mitigated the sensitivity limitations of UV detection, enabling detection at food-safety-relevant concentration ranges. A robust HPLC-UV method was developed with good peak separation within 17 min using a Zorbax SB C8 column (150 × 4.6 mm, 5 µm) with a gradient system consisting of a 20 mM formate buffer (pH 3.0) and an acetonitrile-methanol (1 : 1, v/v) blend. Detection was performed using the dual-wavelength mode at 230 and 275 nm. The procedure met the linearity, repeatability and recovery validation criteria under Commission Implementing Regulation (EU) 2021/808, with recoveries of 77.7-109.2% and expanded measurement uncertainty values not exceeding 42.8%, in accordance with SANTE/11312/2021 v2. The presented sorbent-free workflow provided a validated screening platform accessible in resource-limited settings worldwide.

Mild mitochondrial stress can establish an adaptive state that increases resistance to subsequent injury, but whether such mitohormetic preconditioning can protect the intestine from ischemia-reperfusion (I/R) remains unclear. Here, we investigated doxycycline as a pharmacological inducer of mild mitochondrial stress using murine intestinal I/R and Caco-2 oxygen-glucose deprivation/reoxygenation models. Doxycycline preconditioning attenuated intestinal epithelial and mitochondrial injury in vivo and increased resistance to subsequent OGD/R in vitro. Across a concentration gradient, low-dose doxycycline induced a mild mitochondrial stress response while preserving mitochondrial function, whereas higher exposure shifted the response toward mitochondrial dysfunction, consistent with a mitohormetic transition. Disruption of ATF5 or mitochondrial redox signaling destabilized this adaptive state and weakened doxycycline-mediated protection. Doxycycline also promoted ATF5-associated mitochondria-peroxisome remodeling, while catalase inhibition compromised the accompanying redox and epithelial protection, supporting a functional contribution of peroxisomal redox buffering to the adaptive response. Together, our findings show that doxycycline preconditioning induces mitohormesis that enhances mitochondrial resilience to intestinal I/R, with ATF5-associated mitochondria-peroxisome remodeling contributing to this adaptive response.