Pulsed Therapy and Tachyphylaxis Mechanisms in Chronic Illness Pharmacology

1 Sun et al. 2018 — Swinging Seesaw Model of Time-Dependent Hormesis

Full Citation:: Sun H, Calabrese EJ, Zheng M, Wang D, Pan Y, Lin Z, Liu Y. A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri. Chemosphere. 2018;205:15–23. (Sun et al. 2018)
DOI:: 10.1016/j.chemosphere.2018.04.043
PMID:: 29679784
Study Design:: Dose-time-response in vitro study with mechanistic modeling
Key Findings::
- Proposes a “swinging seesaw” model for time-dependent hormesis
- Stimulatory and inhibitory effects integrate across dose AND time simultaneously
- Low-dose stimulation appearing at one timepoint may be absent or reversed at another
- Model validated across 5 antibacterial chemicals on bioluminescence
Conclusion:: The hormetic dose-response is a 3D volume (dose × time × response), not a 2D curve. Failing to account for time collapses the therapeutic window into a potentially misleading static curve. Central theoretical pillar for time-dependent dosing schedules.
Limitations:: In vitro bacterial model; single organism system; no human or mammalian data.
Certainty:: 0.75

2 Mushak 2016 — Temporal Stability of Chemical Hormesis

Full Citation:: Mushak P. Temporal stability of chemical hormesis (CH): Is CH just a temporary stop on the road to thresholds and toxic responses? Science of the Total Environment. 2016;569–570:1446–1456. (Mushak 2016)
DOI:: 10.1016/j.scitotenv.2016.06.233
PMID:: 27396315
Study Design:: Critical review
Key Findings::
- Many hormetic responses are transitory — appearing at one exposure duration, disappearing with continued exposure
- Temporal stability of hormesis is under-studied and often assumed rather than demonstrated
- Persistent hormesis documented in some specialized cases; transitory in most
- Raises fundamental question: is hormesis a stable phenomenon or a temporary adaptive response that fades?
Conclusion:: If hormesis is transient, continuous drug delivery is inherently self-limiting — the benefit fades. Implies pulsed dosing may be necessary to maintain hormetic benefit over chronic treatment duration. Key theoretical justification for intermittent over continuous dosing.
Limitations:: Focused on environmental toxicology; limited clinical pharmacology data.
Certainty:: 0.65

3 Calabrese 2016 — Preconditioning as Hormesis: Temporal and Mechanistic Frameworks

Full Citation:: Calabrese EJ. Preconditioning is hormesis part II: How the conditioning dose mediates protection: Dose optimization within temporal and mechanistic frameworks. Pharmacological Research. 2016;110:265–275. (Calabrese 2016)
DOI:: 10.1016/j.phrs.2015.12.020
PMID:: 26748033
Study Design:: Systematic review with mechanistic verification
Key Findings::
- The conditioning dose producing maximal mechanism activation was the same dose providing optimal protection against the challenge dose
- Receptor antagonists/inhibitors blocking the conditioning response abolished subsequent protection
- Conditioning responses displayed hormetic dose-response curves
- Temporal optimization is essential: the conditioning dose must precede the challenge dose with correct timing
Conclusion:: Preconditioning-induced protection is directly mediated by hormetic mechanisms with defined temporal profiles. This directly translates to clinical dosing: drug doses must be timed so the hormetic preconditioning window is active when pathology is active. Temporal optimization is as important as dose optimization.
Limitations:: Review of experimental literature; no clinical trials.
Certainty:: 0.75

4 Costa-Neto & Parreiras-E-Silva 2025 — GPCR Tachyphylaxis: Role of Ligand Residence Time

Full Citation:: Costa-Neto CM, Parreiras-E-Silva LT. Deciphering complexity of GPCR signaling and modulation: Implications and perspectives for drug discovery. Clinical Science. 2025;139(10):463–477. (Costa-Neto and Parreiras-E-Silva 2025)
DOI:: 10.1042/CS20245182
PMID:: 40400289
PMCID:: PMC12204005
Study Design:: Comprehensive review of GPCR signaling complexity
Key Findings::
- GPCR tachyphylaxis is governed primarily by ligand dissociation rate (k_off) — high residence time — rather than β-arrestin desensitization alone
- Internalized receptors remain active when bound to high-residence-time ligands, favoring sustained endosomal signaling
- Shorter receptor residence times (intermittent/pulsed delivery) may avoid tachyphylaxis
- Reviews biased agonism, dual agonism, and non-canonical G protein signaling as strategies to modulate tachyphylaxis
Conclusion:: For drugs with high receptor residence time (beta-blockers, H1 antihistamines, LDN), tachyphylaxis may develop via sustained endosomal signaling. Pulsed/intermittent dosing could prevent this by allowing receptor recycling to the surface in a resensitized state. Ligand residence time is a druggable parameter for tachyphylaxis prevention.
Limitations:: Review; no new empirical data.
Certainty:: 0.70

5 Gupta et al. 2018 — GPCR Resensitization Paradigms

Full Citation:: Gupta MK, Mohan ML, Naga Prasad SV. G protein-coupled receptor resensitization paradigms. International Review of Cell and Molecular Biology. 2018;339:63–91. (Gupta, Mohan, and Naga Prasad 2018)
DOI:: 10.1016/bs.ircmb.2018.03.002
PMID:: 29776605
Study Design:: Comprehensive review
Key Findings::
- GPCR function requires coordinated activation → desensitization → resensitization cycling
- Desensitized GPCRs internalize into endosomes where protein phosphatases dephosphorylate them
- Resensitized (dephosphorylated) receptors recycle to the membrane as naive receptors
- The resensitization cycle is exquisitely regulated and has been under-studied vs activation/desensitization
Conclusion:: Receptor resensitization requires a drug-free interval — the time needed for the internalize → dephosphorylate → recycle → return cycle. Continuous dosing fills this interval, preventing the resensitization that would otherwise occur. Provides molecular rationale for drug holidays.
Limitations:: Review; no clinical data.
Certainty:: 0.70

6 Kliewer et al. 2017 — GPCR Dephosphorylation and Resensitization Kinetics

Full Citation:: Kliewer A, Reinscheid RK, Schulz S. Emerging paradigms of G protein-coupled receptor dephosphorylation. Trends in Pharmacological Sciences. 2017;38(7):621–636. (Kliewer, Reinscheid, and Schulz 2017)
DOI:: 10.1016/j.tips.2017.04.002
PMID:: 28478994
Study Design:: Review — GPCR dephosphorylation kinetics and spatial regulation
Key Findings::
- GPCR dephosphorylation starts immediately after activation at the plasma membrane and continues along the endocytic pathway
- Dephosphorylation disrupts receptor-arrestin complexes, terminating arrestin-dependent signaling
- Partially dephosphorylated GPCRs may remain membrane-bound for renewed agonist activation
- Dephosphorylation kinetics set the temporal window for receptor re-availability
Conclusion:: If the dephosphorylation half-life of a receptor target is, e.g., 4–6 hours, then dosing every 4 hours prevents resensitization while dosing every 12 hours allows it. This directly informs optimal pulsing intervals for specific receptor targets — a calculation that has never been systematically applied to ME/CFS pharmacology.
Limitations:: Review; no clinical application data.
Certainty:: 0.70

7 Koch & Höllt 2008 — Opioid Tolerance: Protective Role of Receptor Internalization

Full Citation:: Koch T, Höllt V. Role of receptor internalization in opioid tolerance and dependence. Pharmacology & Therapeutics. 2008;117(2):199–206. (Koch and Höllt 2008)
DOI:: 10.1016/j.pharmthera.2007.10.003
PMID:: 18076994
Study Design:: Comprehensive review — opioid receptor trafficking
Key Findings::
- Paradoxical finding: agonist-induced μ-opioid receptor internalization can REDUCE tolerance in vivo
- Desensitized and internalized receptors are rapidly recycled to the cell surface in a reactivated state
- Opioids with high internalization efficacy produce LESS tolerance than those with low internalization efficacy
- Internalization → dephosphorylation → recycling → resensitization forms a protective cycle
Conclusion:: Receptor internalization — traditionally viewed as the mechanism of tolerance — is actually protective against tolerance by enabling resensitization. This is direct precedent for the model that intermittent drug presence (allowing the full internalize → resensitize cycle) preserves therapeutic responsiveness better than continuous receptor occupancy. Relevant to LDN’s 4–6h opioid blockade window.
Limitations:: Review; opioid-specific.
Certainty:: 0.75

8 Teyani et al. 2024 — ROS-Mediated β2AR Tachyphylaxis

Full Citation:: Teyani RL, Moghaddam F, Moniri NH. ROS-mediated regulation of β2AR function: Does oxidation play a meaningful role towards β2-agonist tachyphylaxis in airway obstructive diseases? Biochemical Pharmacology. 2024;226:116403. (Teyani, Moghaddam, and Moniri 2024)
DOI:: 10.1016/j.bcp.2024.116403
PMID:: 38945277
PMCID:: PMC11301793
Study Design:: Review — β2AR tachyphylaxis, ROS-mediated receptor oxidation
Key Findings::
- β2-agonists exhibit clinical tachyphylaxis over repeated/chronic use
- ROS generated by β2AR activation can oxidize β2AR cysteine residues, producing distinct functional outcomes
- ROS-mediated receptor oxidation is a tachyphylaxis mechanism distinct from canonical arrestin-mediated desensitization
- Oxidative airway microenvironment (disease state) amplifies tachyphylaxis
Conclusion:: Patients with high oxidative burden (ME/CFS) are at elevated risk of drug tachyphylaxis via ROS-mediated receptor oxidation. Pulsed dosing reduces cumulative ROS exposure at the receptor. Provides a pathophysiological rationale for why ME/CFS patients may be especially susceptible to drug tolerance, and why pulsing may be especially beneficial in this population.
Limitations:: Review; focused on airway disease; no ME/CFS or systemic illness data.
Certainty:: 0.65

9 Konopka et al. 2023 — Rapamycin Therapeutic Window: Intermittent Dosing Rationale

Full Citation:: Konopka AR, Lamming DW; RAP PAC Investigators; EVERLAST Investigators. Blazing a trail for the clinical use of rapamycin as a geroprotecTOR. GeroScience. 2023;45(5):2769–2783. (Konopka et al. 2023)
DOI:: 10.1007/s11357-023-00935-x
PMID:: 37801202
PMCID:: PMC10643772
Study Design:: Review and clinical trial preview
Key Findings::
- mTORC1 inhibition promotes healthy aging; mTORC2 inhibition causes metabolic side effects (insulin resistance, immunosuppression)
- Differences in kinetics by which rapamycin inhibits mTORC1 vs mTORC2 suggest a therapeutic window exploitable through intermittent dosing
- RAP PAC and EVERLAST clinical trials actively investigating optimal intermittent schedules in humans
- Alternative rapalogs with more selective mTORC1 inhibition under investigation
Conclusion:: The paradigmatic case of differential target off-rates enabling intermittent over continuous dosing. The principle — differential temporal sensitivities of therapeutic vs adverse targets — generalizes to other drugs: when a drug has one target mediating benefit and another mediating harm, intermittent dosing can exploit their different kinetics.
Limitations:: Review; optimal human intermittent schedules unknown.
Certainty:: 0.75

10 Arriola Apelo et al. 2016 — Intermittent Rapamycin Mitigates Side Effects

Full Citation:: Arriola Apelo SI, Neuman JC, Baar EL, Syed FA, Cummings NE, Brar HK, Pumper CP, Kimple ME, Lamming DW. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system. Aging Cell. 2016;15(1):28–38. (Arriola Apelo et al. 2016)
DOI:: 10.1111/acel.12405
PMID:: 26463117
PMCID:: PMC4717280
Study Design:: In vivo — C57BL/6J mice, daily vs intermittent rapamycin
Key Findings::
- Intermittent rapamycin (2 mg/kg every 5 days) preserved mTORC1 inhibition benefits
- Daily rapamycin caused glucose intolerance, elevated fasting glucose/insulin, and immunosuppression
- Intermittent dosing had minimal effects on glucose tolerance and reduced impact on the immune system
- Everolimus and temsirolimus (rapalogs) also showed better therapeutic windows than daily rapamycin
Conclusion:: Empirical proof that intermittent dosing separates therapeutic from adverse effects when they are mediated by different targets (mTORC1 vs mTORC2) with different temporal dynamics. This is a paradigmatic demonstration that the principle works in vivo. Directly translatable to the 17-drug hormesis framework in ME/CFS.
Limitations:: Mouse study; single drug; mTOR-specific.
Certainty:: 0.80

11 Gile et al. 2026 — Rapamycin Modulates Purine Metabolism and Mitochondrial Energy in ME/CFS

Full Citation:: Gile B, Bulbule S, Toriola MA, Ruan BT, Marium S, Benko A, Grach S, Mueller M, Bateman L, Bell J, Yellman B, Berner J, Chheda B, Kaufman D, Gottschalk G, Roy A. Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study. Journal of Translational Medicine. 2026;24(1):921. (Gile et al. 2026)
DOI:: https://doi.org/10.1186/s12967-026-08575-3
Study Design:: Phase II multicenter observational pilot (n=86 enrolled; 70 completed day 36; 40 completed 90 days). Simmaron/Bateman Horne/Mayo/CCD consortium. No placebo group. NCT06257420.
Key Findings::
- LCMS-based purine metabolomics showed rapamycin differentially regulated IMP→XMP and IMP→hypoxanthine conversion
- Flow cytometry confirmed rapamycin reduces IMP dehydrogenase (IMPDH) activity, limiting IMP→XMP flux
- Purine supplementation induced mitochondrial oxidative stress in PBMCs; rapamycin mitigated this
- Seahorse OCR: mitochondrial respiration improved in responder PBMCs after 90 days of rapamycin
- Reduced microglial inflammatory responses in flow cytometry assays
- Clinical symptom improvement consistent with prior Ruan 2025 pilot
Conclusion:: First mechanistic evidence linking rapamycin’s clinical benefit in ME/CFS to purine metabolism modulation — mTORC1 inhibition → reduced IMPDH activity → altered purine biosynthesis → improved mitochondrial respiration → reduced microglial inflammation. Establishes a purine-mediated mTOR→mitochondria→microglia axis.
Limitations:: Uncontrolled (no placebo); molecular results biased to responders; 53% attrition at 90 days; same consortium as prior rapamycin studies (potential for correlated bias). No blinding. Purine metabolism mechanism requires independent replication.
Certainty:: 0.50

12 Fronticelli Baldelli and Buonsenso 2025 — mTOR Hyperactivation in Pediatric Post-Infectious Syndromes

Full Citation:: Fronticelli Baldelli G, Buonsenso D. Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links. Children. 2025;12(12):1603. (Fronticelli Baldelli and Buonsenso 2025)
DOI:: https://doi.org/10.3390/children12121603
Study Design:: Narrative review — clinical, translational, and experimental literature synthesis
Key Findings::
- Proposes mTOR as mechanistic link between peripheral infection-driven inflammation and CNS dysfunction in post-infectious syndromes
- Stepwise pathway: sustained mTOR activation→T-cell/macrophage pro-inflammatory skew→BBB endothelial compromise→microglial/neuronal mTOR activation→neuroinflammation, impaired synaptic maintenance, neurotransmitter disruption
- Framework applies to Long COVID, ME/CFS, and PANS/PANDAS in children
- mTORS6 phosphorylation as candidate biomarker for pathway activation
- Motivates mTOR-targeted interventions (rapamycin) in pediatric post-infectious neuropsychiatric syndromes
Conclusion:: Extends the mTOR hyperactivation framework to pediatric populations. Reinforces the infection→mTOR→BBB→neuroinflammation cascade proposed in adult ME/CFS literature (Bar-Tana 2025, Drosen 2025). Pediatric focus is novel.
Limitations:: Review only — no primary human data. Pediatrics-focused; adult ME/CFS translational relevance inferred but not directly tested. mTOR→psychiatric symptoms link is plausible but many steps lack pediatric human evidence. Single-proponent model (Fronticelli Baldelli). Journal quality: MDPI Children (impact factor ~2.5).
Certainty:: 0.35

13 Hodding et al. 1980 — Drug Withdrawal Syndromes: Foundational Review

Full Citation:: Hodding GC, Jann M, Ackerman IP. Drug withdrawal syndromes — a literature review. Western Journal of Medicine. 1980;133(5):383–391. (Hodding, Jann, and Ackerman 1980)
PMID:: 7008358
PMCID:: PMC1272349
Study Design:: Literature review — drug withdrawal syndromes
Key Findings::
- Sedative-hypnotics, opiates, corticosteroids, clonidine, tricyclic antidepressants, and beta-adrenergic blocking agents meet criteria for withdrawal syndromes
- Defines criteria for identifying true withdrawal syndromes: (1) consistently observed, (2) dose- and duration-dependent, (3) preventable by gradual tapering, (4) not attributable to underlying disease
- Gradual tapering recommended for all drugs meeting criteria
Conclusion:: The risk counterpart to pulsed therapy: some drugs with tachyphylaxis also have dangerous withdrawal/rebound syndromes if stopped abruptly. Any pulsed-therapy framework must account for withdrawal risk — gradual tapering vs rapid pulsing are opposite strategies, and the framework must determine which applies. Corticosteroids and beta-blockers are on this list — both in the ME/CFS 17-drug framework.
Limitations:: Dated 1980; review-level only; Western J Med (moderate-impact journal); no quantitative meta-analysis.
Certainty:: 0.50

14 Papp et al. 2021 — Proactive Pulse Therapy in Psoriasis

Full Citation:: Papp KA, Dhadwal G, Gooderham M, Guenther L, Turchin I, Wiseman M, Yeung J. Emerging paradigm shift toward proactive topical treatment of psoriasis: A narrative review. Dermatologic Therapy. 2021;34(6):e15104. (Papp et al. 2021)
DOI:: 10.1111/dth.15104
PMID:: 34418251
PMCID:: PMC9286633
Study Design:: Narrative review — proactive/pulse maintenance therapy
Key Findings::
- Emerging evidence supports a paradigm shift toward proactive treatment once skin is completely clear
- Chronic continuous topical corticosteroids carry safety concerns that proactive pulse therapy mitigates
- Pulse/proactive maintenance preserves therapeutic benefit while reducing cumulative drug exposure
- Discusses transition strategies from acute to maintenance pulse therapy
Conclusion:: Direct clinical precedent for “pulse therapy” paradigm in a chronic inflammatory disease. Psoriasis is an autoimmune/inflammatory chronic condition — conceptually analogous to the inflammatory maintenance problem in ME/CFS. The success of proactive/pulse therapy in dermatology provides a translational template.
Limitations:: Narrative review (not systematic); dermatology-specific; industry-funded authors.
Certainty:: 0.55

15 Son et al. 2008 — Hormetic Dietary Phytochemicals via Nrf2/ARE

Full Citation:: Son TG, Camandola S, Mattson MP. Hormetic dietary phytochemicals. NeuroMolecular Medicine. 2008;10(4):236–246. (Son, Camandola, and Mattson 2008)
DOI:: 10.1007/s12017-008-8037-y
PMID:: 18543123
PMCID:: PMC2635914
Study Design:: Review — hormesis mechanisms of dietary phytochemicals
Key Findings::
- Phytochemicals (sulforaphane, curcumin, resveratrol) activate adaptive stress responses at subtoxic doses
- Nrf2/ARE pathway identified as prototypical hormetic neuroprotective mechanism
- Adaptive cellular stress response pathways (sirtuin-FOXO, NF-κB, Nrf2/ARE) mediate hormetic benefits
- “Noxious” properties of phytochemicals at low doses trigger beneficial adaptive responses = pharmacological hormesis
Conclusion:: Nrf2 activators (sulforaphane, NAC, quercetin in the ME/CFS framework) operate via hormetic mechanisms. Continuous high-dose administration may exhaust the adaptive Nrf2 response (Keap1 degradation, negative feedback via GSK3β). Implies pulsed low-dose may sustain Nrf2-mediated benefit better than continuous high-dose — a hypothesis directly testable in the ME/CFS framework.
Limitations:: Review; 2008 (dated); no clinical dosing studies.
Certainty:: 0.55

References

Arriola Apelo, Sebastian I, Joshua C Neuman, Emma L Baar, Faizaan A Syed, Nicole E Cummings, Harpreet K Brar, Cassidy P Pumper, Michelle E Kimple, and Dudley W Lamming. 2016. “Alternative Rapamycin Treatment Regimens Mitigate the Impact of Rapamycin on Glucose Homeostasis and the Immune System.” Aging Cell 15 (1): 28–38. https://doi.org/10.1111/acel.12405.

Calabrese, Edward J. 2016. “Preconditioning Is Hormesis Part II: How the Conditioning Dose Mediates Protection: Dose Optimization Within Temporal and Mechanistic Frameworks.” Pharmacological Research 110: 265–75. https://doi.org/10.1016/j.phrs.2015.12.020.

Costa-Neto, Claudio M, and Lucas T Parreiras-E-Silva. 2025. “Deciphering Complexity of GPCR Signaling and Modulation: Implications and Perspectives for Drug Discovery.” Clinical Science 139 (10): 463–77. https://doi.org/10.1042/CS20245182.

Fronticelli Baldelli, Giovanni, and Danilo Buonsenso. 2025. “Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.” Children 12 (12): 1603. https://doi.org/10.3390/children12121603.

Gile, Brooke, Sarojini Bulbule, Mubaraq A. Toriola, Brian T. Ruan, Shabnam Marium, Anna Benko, Stephanie Grach, et al. 2026. “Association of Rapamycin Treatment with the Modulation of Purine Metabolism, Reduced Microglial Inflammatory Responses, Improved Mitochondrial Energy Metabolism, and Alleviation of Fatigue Symptoms in ME/CFS Subjects: Pilot Findings from Phase-II Observational Study.” Journal of Translational Medicine 24 (1): 921. https://doi.org/10.1186/s12967-026-08575-3.

Gupta, Manveen K, Maradumane L Mohan, and Sathyamangla V Naga Prasad. 2018. “G Protein-Coupled Receptor Resensitization Paradigms.” International Review of Cell and Molecular Biology 339: 63–91. https://doi.org/10.1016/bs.ircmb.2018.03.002.

Hodding, George C, Michael Jann, and Irving P Ackerman. 1980. “Drug Withdrawal Syndromes — a Literature Review.” Western Journal of Medicine 133 (5): 383–91.

Kliewer, Andrea, Rainer K Reinscheid, and Stefan Schulz. 2017. “Emerging Paradigms of G Protein-Coupled Receptor Dephosphorylation.” Trends in Pharmacological Sciences 38 (7): 621–36. https://doi.org/10.1016/j.tips.2017.04.002.

Koch, Thomas, and Volker Höllt. 2008. “Role of Receptor Internalization in Opioid Tolerance and Dependence.” Pharmacology & Therapeutics 117 (2): 199–206. https://doi.org/10.1016/j.pharmthera.2007.10.003.

Konopka, Adam R, Dudley W Lamming, RAP PAC Investigators, and EVERLAST Investigators. 2023. “Blazing a Trail for the Clinical Use of Rapamycin as a GeroprotecTOR.” GeroScience 45 (5): 2769–83. https://doi.org/10.1007/s11357-023-00935-x.

Mushak, Paul. 2016. “Temporal Stability of Chemical Hormesis (CH): Is CH Just a Temporary Stop on the Road to Thresholds and Toxic Responses?” Science of the Total Environment 569-570: 1446–56. https://doi.org/10.1016/j.scitotenv.2016.06.233.

Papp, Kim A, Gurbir Dhadwal, Melinda Gooderham, Lyn Guenther, Irina Turchin, Marni Wiseman, and Jensen Yeung. 2021. “Emerging Paradigm Shift Toward Proactive Topical Treatment of Psoriasis: A Narrative Review.” Dermatologic Therapy 34 (6): e15104. https://doi.org/10.1111/dth.15104.

Son, Tae Gen, Simonetta Camandola, and Mark P Mattson. 2008. “Hormetic Dietary Phytochemicals.” NeuroMolecular Medicine 10 (4): 236–46. https://doi.org/10.1007/s12017-008-8037-y.

Sun, Haoyu, Edward J Calabrese, Min Zheng, Dali Wang, Yong Pan, Zhifen Lin, and Ying Liu. 2018. “A Swinging Seesaw as a Novel Model Mechanism for Time-Dependent Hormesis Under Dose-Dependent Stimulatory and Inhibitory Effects: A Case Study on the Toxicity of Antibacterial Chemicals to Aliivibrio Fischeri.” Chemosphere 205: 15–23. https://doi.org/10.1016/j.chemosphere.2018.04.043.

Teyani, Rabia L, Fatemeh Moghaddam, and Nader H Moniri. 2024. “ROS-Mediated Regulation of β2AR Function: Does Oxidation Play a Meaningful Role Towards β2-Agonist Tachyphylaxis in Airway Obstructive Diseases?” Biochemical Pharmacology 226: 116403. https://doi.org/10.1016/j.bcp.2024.116403.